CLMAN 2- Midterm- Renal, Anemias, Cancer

Glomular filtration rate equation

Common methods to estimate theGFR in adults utilize serum creatinine concentration, creatinine clearance, and estimation equations Since all renal disorders variably affect renal function, estimation of theGFR has no diagnostic utility Reduction inGFR implies either progression of the underlying disease or the development of a superimposed and often reversible problem such as decreased renal perfusion due to volume depletion Increase inGFR, is indicative of improvement in renal function StableGFR in patients with renal disease implies stable disease

Renal Disease Assessment

Kidney Disease: Acute or Chronic?? AKI/ARF-Acute Kidney Injury/Acute Renal Failure: Worsening renal function over hours to days CKD-Chronic kidney disease: Deteriorating renal function over months to years Urinalysis w/ microscopic exam of urinary sediment: Most important noninvasive test for diagnostic evaluation Characteristic findings suggesting certain diagnoses: muddy brown granular casts and epithelial cell casts in a pt w/ARF highly suggestive of acute tubular necrosis (ATN) one red cell cast is diagnostic of vasculitis or glomerulonephritis significant proteinuria indicative of some form of glomerular disease Morphology of RBCs is diagnostic: -Uniform, round red cells c/w extrarenal bleeding -Red cells w/ dysmorphic appearance is c/w renal lesions, particularly glomerular diseases. *Red Blood Cell Casts: Glomerularnephritis *Pigmented granular cast: seen in acute tubular necrosis *Renal Tubular epithelial cell cast: seen in renal tubular injury

1) Which of the following is true concerning colorectal cancer?

a) Most colorectal cancers are found during rectal examination b) Rectal carcinoma is more common than cancers involving the colon c) Early manifestations include abdominal pain and cramping d) Later disease presentation often includes iron deficiency anemia.

1) A 65 year old Hispanic woman has a history of type 2 diabetes. A routine urinalysis reveals a few epithelial cells and is negative for leukocytes, nitrites, and protein. The serum creatinine is 1.5 mg/dL. Which of the following actions would you recommend next?

a) Order a urine test for culture and sensitivity b) Order a spot urine for microalbumin to creatinine ratio c) Because the urinalysis is negative, no further tests are necessart d) Recommend a screening intravenous pyelogram

1) A 68 year old man presents with suspected bladder cancer. You consider that its most common presenting sign or symptom is:

a) Painful urination b) Fever and flank pain c) Painless gross hematuria d) Palpable abdominal mass

1) All of the following can cause an increased PSA except:

a) Prostate infection b) Cystoscopy c) BPH d) Prostatectomy

1) A 52- year old woman who has had Type 2 diabetes for 15 years is concerned about her kidneys. She has a history of three urinary tract infections within the past 8 months, but is currently asymptomatic. Which of the following is the best course to follow?

a) Recheck urine during the visit, send a urine specimen for culture and sensitivity, and refer to a nephrologist b) Order a urinalysis dipstick test to be repeated monthly c) Order a CT scan of the kidneys d) Provide empiric treatment for UTI

1) You see a 33 year old woman whose Pap smear result reveals atypical cells of undetermined significance (ASC-US). She is also positive for HPV, with genotype testing revealing the presence of HPV type 16. You recommend:

a) Repeating Pap test immediately b) Repeating the Pap test in 3 to 4 months c) Referral for colposcopy d) Administering the HPV vaccine

1) You would recommend the pneumococcal vaccine to patient with all of the following conditions except:

a) Sickle cell anemia b) Splenectomy c) HIV infection d) G6PD deficiency anemia

1) Which of the following is the best advice on taking ferrous sulfate to enhance iron absorption?

a) Take with other medications b) Take on a full stomach c) Take on an empty stomach d) Do not take with vitamin C

1) A patient who has been prescribed warfarin sodium (Coumadin) is advised to avoid eating large amounts of leafy green vegetables because:

a) The high vitamin K levels will decrease the INR b) They have too much ascorbic acid, which can interact with the medicine c) The high fiber content will decrease the absorption of the warfarin d) The vitamins in the vegetables will bind with, and inactivate, the warfarin

1) Common causes of chronic renal failure include all of the following except:

a) Type 2 diabetes b) Recurrent pyelonephritis c) Hypotension d) Polycystic kidney disease

renal tubular epithelial cell cast

renal tubular injury

pigmented granular cast

tubular necrosis

colon cancer

§ 3rd leading cause of cancer death both genders § Most are adenocarcinoma § Colon - 70% § Rectal - 30% Risk Factors § IBD § Hx of neoplasia § > 50 y/o § FH of colorectal Cancer § Familial polyposis syndrome § Some studies show use of antioxidants, calcium supplement and low dose aspirin may reduce risk. Presentation § Usually asymptomatic until disease is advanced § Vague abdominal complaints § Iron deficient anemia § Mass often beyond digital exam § American Cancer Society does not recommend FOBT from rectal exam as appropriate screening § Recommend at home FOBT from 3 consecutive specimens: Colonoscopy if results are positive § Colonoscopy screening beginning at 50 y/o, every 10 years § Alternative: flexible sigmoidoscopy, Barium enema, CT colonography every 5 years. § Interval between scopes is effected by personal history, family history and findings on prior colonoscopy Treatment: § Surgery § Chemotherapy § Radiation Therapy § Prognosis: stage and overall health of patient

Bladder Cancer

§ 6th most common type of cancer in US § 2nd most common urologic malignancy after prostate. Usually later in life, mean age at Dx = 65 y/o § Men > Women Risk factors: - #1 Cigarette smoking!!! - Family history - Exposure: industrial chemicals (paints, dyes, solvents), arsenic - Medications: cyclophosphamide, pioglitazone (Actos) Presentation: -#1Gross painless hematuria - Persistent microscopic hematuria ( about 20%) - Irritative voiding symptoms, urinary frequency w/o fever (much less common) Diagnosis and Staging § Urology - cystoscopy with biopsy § Most common pathology: urothelial cell carcinoma § Stage is based on TNM § Cell characteristics, depth of extension Treatment § Superficial: transurethral resection & intravesicular chemotherapy § Surgery: depends on depth of invasion, stage § TUR to Partial cystectomy to radical cystectomy § Radiation Therapy - advanced stages § Systemic Chemotherapy and/or immunotherapy - advanced stages, metastasis

esophageal cancer

§ Usually develops between 50-70 y/o § Men to Women are 3:1 § Two histologic types § Squamous cell § Adenocarcinoma § In US § Squamous cell more common among Black Americans § 90% in distal 2/3 of esophagus § Chronic alcohol & tobacco use strongly associated with increased risk of squamous cell § Adenocarcinoma more common among White Americans § Incidence increasing - now more common than squamous cell § Majority develop from Barrett metaplasia d/t chronic GERD § Most in the distal 1/3 of esophagus § Obesity strongly associated with increased risk Treatment Curable: superficial, early stage § Surgery: Esophagectomy or Endoscopic mucosal resection of Tis and T1a cancers § Chemotherapy: adjuvant or neoadjuvant to surgery and/or Concurrent with radiation § Radiation Therapy: Adjuvant or neoadjuvant and/or Concurrent with chemotherapy § Incurable: § No surgery § Chemotherapy or Chemoradiation § Palliation of esophageal obstruction § Radiation alone?

esophageal cancer

§ Usually develops between 50-70 y/o § Men to Women are 3:1 § Two histologic types: Squamous cell § Adenocarcinoma § In US: -Squamous cell more common among Black Americans and 90% in distal 2/3 of esophagus. Chronic alcohol & tobacco use strongly associated with increased risk of squamous cell -Adenocarcinoma more common among White Americans. Incidence increasing - now more common than squamous cell § Majority develop from Barrett metaplasia d/t chronic GERD § Most in the distal 1/3 of esophagus § Obesity strongly associated with increased risk

FXaI: Edoxaban (Lixiana, Savaysa)

• T1/2 = 10 to 14 hrs • Indication: o Prevention and treatment of VTE o Stroke prevention in pt w/ A Fib • Do not use in pregnancy or patients with prosthetic heart valves • Dosing o Fixed dose without monitoring o 30mg or 60 mg daily • 60 mg for stroke prevention or treatment of VTE • 30 mg daily if weight < 60kg or with P-glycoprotien inhibitors • Dose reduce if CC 15-50 mL/min - • Not recommended if CC <15mL/min or > 95 mL/min • Labs prior to use: platelet count, PT, aPTT, serum creatinine, liver function tests • Black Box Warning with neuraxial anesthesia

TI: Bivalirudin (Angiomax)

• Indications: o Percutaneous coronary interventions o HIT • Dose: o 0.75mg/kg IV bolus then 1.75mg/kg/hr o CC < 30mL/min rate of 1 mg/kg/hr • T1/2 o 25 minutes o Coagulation returns to normal at about 1 hr after d/c • Monitor o Activated clotting time (ACT) o aPTT - target 1.5-2.5 x normal

TI: Argatroban (Arganova, Argaron, Argtra...)

• Indications: o Percutaneous coronary interventions (PCI) o HIT - with normal hepatic function • Dose: o PCI: 350 mcg/kg bolus over 3-5 hrs, infuse 25mcg/kg/min o HIT: 2 mcg/kg/min IV • T1/2 o 40-50 minutes • Monitor o Activated clotting time (ACT) for PCI o aPTT - target 1.5- 3 x normal for HIT • Lower dose for hepatic impairment • Prolongs PT/INR - if switching to warfarin may need to adjust INR range until argatroban is d/c'd

Anticoag timing

• Once its decided that the anticoagulant needs to be stopped due to bleeding risk - timing is determined by the pharmacokinetics of the agent • Warfarin: o d/c 5 days prior to surgery o Check INR day of surgery - want < 1.4 o Restart12-24 hours after surgery o May be a span of 8 days of subtherapeutic anticoagulation o Bridge if high to very high risk of thromboembolic event • Dabigatran: o DC 2-3 days before procedure or up to 4 days prior if renal impairment o Bridging usually only for very high risk of thromboembolic event o Restart 24 hrs after for low bleed risk, 48-72 hours for higher bleeding risk • Rivaroxaban, Apixaban & Edoxaban: o DC 2-3 days before procedure o Rapid offset obviates need to bridge o Restart 24 hrs after for low bleed risk, 48-72 hours for higher bleeding risk

TI: Dabigatran (Pradaxa)

• Only oral DTI - prodrug converted in liver • Indications: o VTE prophylaxis and management o Stroke prevention in A Fib • Dose: o VTE in surgical patient: 110 mg 1-4 hrs after Sx, then 220 mg daily for 28-35 days (hip) or 10 days (knee) o VTE treatment, 2ndary prevention: 150mg bid (CC>30mL/Min) o Stroke prevention in Afib: 110 to 150 mg bid • Dose reduce by about 50% for CC<30 mL/min) • T1/2 o 12-17 hours if normal renal function • P-glycoprotein interaction o Inducers (rifampin) - avoid - reduces anticoagulant effect o Inhibitors (verapamil, ketoconazole) - With renal failure - may increase anticoagulation • Avoid if BMI > 40 kg/m2 • Lab Testing o Before initiating: platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), serum creatinine o Routine monitoring of coagulation times not required o If necessary to test for dabigatran effect (eg emergent surgery) - Ecarin clotting time best method - not widely available - Dilute thrombin time (dilute TT) - aPTT - Activated clotting time (ACT) - PT NOT a reliable measure, don't use point of care PT/INR devices • Can use Idarucizumab - I-Dare-U-cizumab an anti dabigatran monoclonal antibody for emergent reversal • Black box warning: no neuraxial anesthesia d/t hematoma • Dyspepsia is common and may limit use

Advantages of heparin/warfarin over DOACS

• Prosthetic heart valves • Pregnancy • Renal impairment • Antiphospholipid syndrome: Little data on efficacy of DOACs • Compliance: Missing one or two doses can result in subtherapeutic anticoagulation • GI disease: Especially those with a history of bleeding d/t no direct antidote • Cost

AKI: Prerenal Azotemia

Most common cause ofAKI/ARF: 40‐80% of cases Can lead to intrinsic renal failure Secondary to renal hypoperfusion via 3 mechanisms 1 . Decreased intravascular volume 2. Change in vascular resistance 3. Decreased cardiac output Causes of volume depletion: Hemorrhage GI losses Dehydration Over diuresis Extravascular sequestration Pancreatitis, trauma, burns, peritonitis

AKI differentials

Recent onset of s/s (fever , discolored urine) suggests acute process. Oliguria/anuria suggests an acute component, - prolonged oliguria (urine < 500 mL/day) consistent w/ advanced renal failure. Steady rise in plasma creatinine (after initial eval) indicates acute or rapidly progressive disease, stable S.Cr consistent w/ chronic disease Rate of rise in the plasma creatinine concentration can assist in differential diagnosis - Progressive rise > 0.3 to 0.5 mg/dL - more likely ATN - Slow rise w/ fluctuations‐ more likely prerenal Radiologic examination : - renal ultrasound reveal small kidneys → c/w chronic disease secondary to progressive loss of renal parenchyma and increased interstitial fibrosis over time - Normal‐sized kidneys does not exclude chronic disease.

The aging kidney

Renal mass declines progressively after the fourth decade Renal blood flow decreases with a resultant increase in arteriolar resistance: allows for an increased filtration fraction and a relative sparing of theGFR After age 40, GFR declines at a rate of approx.0.8 mL/min: (though some older patients show little or no change) Serum creatinine values relatively constant because of decreased muscle mass along with the decrease inGFR. GFR impairment is partially due to thickening of theGBM, leading to glomerulosclerosis

Renal Vascular Disease

*Cause of both acute and chronic renal disease Vascular diseases affecting the kidney can be divided into those that produce acute or chronic disease Acute: Major acute renal vascular disease is most commonly vasculitis (Wegener's granulomatosis) Less commonly: thromboembolic disease, hemolytic‐uremic syndrome or thrombotic thrombocytopenic purpura (HUS/TTP), malignant hypertension, and scleroderma. Chronic: Nephrosclerosis Unilateral or bilateral renal artery stenosis Cholesterol related atherosclerotic/embolic disease

lung Cancer

-85% die of disease -95% of lung cancer from Smoking! -Even 15 years after cessation are 4x more likely than never-smoker § Asbestos § Radon § Often present with non specific c/o: Cough, dyspnea, chest pain, hemoptysis, weight loss § X-ray Types: -Small cell -Non small cell (NSCLC) § Adenocarcinoma § Squamous cell carcinoma § Large cell undifferentiated § Brochoalveolar § Unspecified Staging: § Non-Small Cell: Uses TNM systems § Small cell: -Limited: one hemithorax, mediastinal, hilar or supraclavicular area -Extensive: any disease outside the above limited area Stage prognostic of survival § Median survival for stage IV 8 - 10 months § Treatment is determined by Histology/Stage § Surgery § Chemotherapy § Radiation Screening: Annual low dose chest CT for: -Current smokers with 30 pack/year history -Former smokers who have been quit < 15 years Annual CT is not recommended for: -Former smokers quit > 15 years -Patients with comorbid conditions that preclude them from having surgery

hemolytic anemia: Paroxysmal Nocturnal Hematuria

-An acquired stem cell disorder -Red blood cells become sensitive to complement which causes lysis Patients have episodic hematuria, typically brown tinged urine in am -Also prone to thrombosis -Can progress to aplastic anemia, myelodysplasia or AML (acute myeloid leukemia) -Anemia varies in severity -May or may not see Reticulocytosis Urine hemosiderin is useful LDH may be elevated -May see iron deficiency Best test is flow cytometry: CD59 and CD55 will be deficient on RBC Treatment: ◦Iron replacement ◦ Prednisone ◦ Blood transfusion ◦ Hematologist

Hemolytic anemia: sickle cell

-Autosomal recessive -Mutation of the β globin chain of Hgb. ◦ Designated HgbS (α2β2 s ) ◦ Those homozygous for mutation have sickle cell anemia (also noted as HbSS) ◦ Those heterozygous for mutation have sickle cell trait (also noted as HbAS) -1 in 10 American black will have the trait -1 in 100 Hispanic will have the trait -≈ 1 in 4-500 American black children will be born with HbSS -HgbS is unstable and when exposed to acidosis or oxidative stress( hypoxia) the cell sickles -The sickling is permanent -These cells cannot change their shape which prevents them from passing through narrow capillaries. Sickled cells survive between 10 - 20 days Laboratory Findings Hct 20-30%, Hgb 8-10 Peripheral smear ◦ Sickled cells ◦ Target cells ◦ Howell-Jolly bodies -Reticulocytosis -Nucleated RBC -WBC elevated (12-15K) -Dx confirmed by Hgb electrophoresis ◦ In homozygous: Hgb S will be predominant, no HgbA, Hgb F varies Signs & Symptoms Painful attacks ◦ Infection, dehydration, hypoxia -Jaundice (hemolysis) -Pigment gallstones -Splenomegaly -Poorly healing ulcers over lower tibia -Severe anemia -Hemolytic , aplastic crisis PE: Episodes last hours to days Vaso occlusion ◦ CVA (some silent), ◦ organ damage (heart, lung, liver), ◦ osteonecrosis, ◦ renal tubular concentrating defect, ◦ Retinopathy that can progress to blindness ◦ Pulmonary hypertension (poor prognosis) ◦ Acute Chest Crisis ◦ Splenic sequestration crises Management -Folic Acid 1mg/day for life -Children from birth to 5 years old may be on prophylactic penicillin daily -Malaria prophylaxis (uniquely vulnerable): HgbAS are protected against -Malaria Pneumococcal Vaccine -Crises episodes are treated symptomatically ◦ Hydrate ◦ Opioids or NSAIDS ◦ Antibiotics (particularly with acute chest crisis) ◦ Oxygen ◦ Hydroxyurea (increases HgbF) 500-750mg/d ◦ Blood transfusion / Blood exchange transfusion ◦ Bone marrow transplant in children

Hemolytic Anemia: G6PD

-G6PD (Glucose-6- Phosphate Dehydrogenase) -Deficiency Hereditary enzyme defect (X-linked recessive) -Episodic hemolytic anemia ◦ With oxidative stresses -When Hgb is oxidized it denatures and forms a precipitant : Heinz bodies Heinz bodies damage the cell membrane -Cells are prematurely removed by spleen (reticuloendothelial cells) -Many variants of disorder that have varying severity Signs & Symptoms ◦Usually healthy ◦ Hemolysis only with oxidative stress ( infection or drug exposure) ◦ Common causative drugs: dapsone, primaquine, quinidine, quinine, sulfonamides, macrodantin ◦ Episodes are self limiting Lab Findings: ◦Normal between episodes ◦ During episodes -Reticulocytosis -Increased indirect bilirubin (jaundice) -Blood smear nondiagnostic but may show bite cells or blister cells -Heinz bodies ◦G6PD assay ◦ May be low, but misleading at or directly after episode when the enzyme deficient group of cells has been removed. ◦ Should be repeated several weeks after hemolysis resolves

Macrocytic Anemia: Alcohol induced

-Macrocytic, typically not Megaloblastic -Anemia from several factors: ◦ If Interferes with absorption of folic acid (megaloblastic) ◦ If Interferes with Hgb synthesis: (sideroblastic anemia) ◦ If Interferes with erythropoiesis (Macrocytosis) ◦ The anemia's reverse with abstinence from alcohol within weeks.

Oncologic Emergencies

-Paraneoplastic syndromes: - Hypercalcemia (NSCLC) -SIADH (SCLC) -Spinal cord compression -Superior Vena Cava Syndrome (SVC syndrome) -Neutropenic Fever Hypercalcemia -Several mechanisms:Less calcium stored in bones, more in plasma, less excreted through kidneys -May see in breast cancer, lung cancer and multiple myeloma -Remember calcium is bound to albumin so if the patients albumin is <4mg/dl you need to calculate a corrected calcium. Mild < 12mg/dl nausea, poor appetite, vomiting and constipation may be present with mild increases in blood calcium levels. Moderate 12 to 14 mg/dl fatigue or excessive tiredness. Heart rhythm abnormalities, increased urinary frequency, and kidney stones may also be present. Severe > 14 mg/dl critically high muscle twitching, anxiety, depression, personality changes and confusion, excessive sleepiness, coma even death may occur. -The severity of symptoms for hypercalcemia depends not only on how high the calcium level is, but also on how fast the rise in serum calcium has occurred. Spinal Cord compression Typically present with "back pain": Not relieved by rest, "deep", Neurologic compromise, Progressive -10 to 40% are not yet diagnosed with cancer -This is a true Emergency: Permanent paralysis, incontinence, significant impairment Cannot delay even one day! Tx: Glucocorticoids, surgical consideration, radiation therapy Superior vena cava syndrome -SVC Major vessel for draining venous blood from head, neck, upper extremities and upper thorax -Rarely life threatening (unless trachea is involved) but should be addressed quickly -80% of patients with SVC will be due to cancer -Most common tumors: Lung then Lymphoma Neutropenic Fever -Neutropenia ANC < 1000: High risk of serious bacterial infection if ANC is < 500 -Neutropenic Fever: Temperature of 38 C(100.4F)degree twice or 38.5 C(101.3F) degrees once in a patient with ANC <1000 -This poses a life threatening emergency and an infection not treated can result in death within 24 hours. Tx: -Empiric Abx -Cultures and more cultures -Blood, urine, throat, sputum, rectal, perhaps even LP -Careful history and physical -Inflammatory signs may be blunted! -Tailor Abx to culture results May give G-CSF

Coagulopathy H & P for Pre-Op

Ask patient: • Easy bruising? • Gums bleeding? Nose bleeds? • Prolonged bleeding after procedures (dental) • Menorrhagia • Previous operative bleeding? • Meds: ASA, NSAIDS, Plavix, Coumadin etc • Any prior blood clots • FAMILY HISTORY!!! • Levels of concern • Minor: Negative history, minor procedure planned, no screening tests • Moderate: Negative history, major procedure planned (with significant bleeding typically associated), Labs: platelets, PT-INR, aPTT, peripheral smear • Considerable: Hx suggests poor hemostasis, large procedure with 'raw' surface left and/or impairs hemostasis (ie cell saver). Labs: platelet count, Pt-INR, aPTT, bleeding time • Great: Hx highly suggestive, Heme Consult!! Be particularly cognizant with patients who have: • Liver disease • Renal failure • Obstructive jaundice • Possible/ known disseminated malignancy

Renal Autoregulation

Autoregulation is the maintenance of a near normal intrarenal hemodynamic environment (RBF, GFR) despite large changes in the systemic blood pressure Vasodilators PGs Kinins NO ANP Vasoconstrictors Renin Angiotensin II Endothelin ADH Renal autoregulation failure: Renal autoregulation breaks down as MAP falls <80 mm Hg, Adjustments in intra-renal hemodynamics are unable to maintain RBF and GFR Hallmark of ARF After age 30, RBF/ GFR ↓ progressively w/ age 80 y/o is nearly half of that of a 20 y/o Failure to decrease arteriolar resistance: Structural changes in renal arterioles and small arteries: Old age, Atherosclerosis Chronic HTN, Malignant or accelerated HTN CKD Reduction in vasodilatory prostaglandins: NSAIDs Cox 2 inhibitors Afferent glomerular arteriolar vasoconstriction caused by: Sepsis Hypercalcemia Hepatorenal syndrome Cyclosporine or tacrolimus Radiocontrast agents Failure to increase efferent arteriolar resistance: ACEI Angiotensin-receptor blockers Renal - artery stenosis

Hemolytic Anemia

Classified as ◦ Intrinsic (d/t components of cell, usually hereditary) ◦ Extrinsic (immune, microangiopathic) Common features: ◦ Haptoglobin ◦ Hemoglobinemia ◦ Increased indirect bilirubin ◦ Increased total bilirubin (4mg/dL) ◦ Increased LDH Types: 1. G6PD 2. Sickle Cell 3. Paroxysmal Nocturnal Hematuria

Disseminated Intravascular Coagulation

Concurrent thrombosis and hemorrhage • Complication of underlying illness affecting approximately 1% of hospital admits • Includes: • Exposure to procoagulants (ie tissue factor, cancer procoagulant): Massive generation of Thrombin = triggered coagulation • Formation of fibrin within the circulation: Widespread intravascular fibrin deposition = tissue ischemia & microangiopathic hemolytic anemia • Fibrinolysis • Depletion of clotting factors • End-organ damage Diagnosing DIC • Suspect b/c of history (ie sepsis, trauma, malignancy), clinical presentation, thrombocytopenia ( < 100K), microangiopathic changes on peripheral blood smear - helmet cells, schistocytes) • Lab confirmation if • Increase thrombin generation ie. Decreased fibrinogen • Increased fibrinolysis ie elevated FDPs and D-dimer • Labs: • FDP (fibrin degradation products) = D-dimer: not specific to for DIC, will be elevated with degradation of cross linked fibrin • PT (prolonged), Fibrinogen (low in acute decompensated DIC BUT it's an acute phase reactant) ,assays to monitor Factors V and VIII (decreased) Treatment • High mortality (40 to 80%) DIC -vs- underlying disorder? • Platelet transfusion if counts are < 20,000 to 50,000 AND bleeding • If bleeding with increased INR and fibrinogen <50mg/dl should get cryoprecipitate (fibrinogen) or FFP • Heparin is used very judiciously to interrupt the underlying coagulopathy - no controlled trials • Protein C if deficiency known • Recombinant human factor VIIa • Treat The Underlying Disease!!!!

Megaloblastic Macrocytic Anemia: B12 (Cobalamin) deficiency

Daily absorption of B12 is about 5 mcg Liver stores 2000-5000mcg ◦ Can take up to 3 years to deplete Causes: ◦Inadequate intake ◦ Strict Vegan ◦Inadequate absorption ◦ Blind loop syndrome, celiac sprue, Crohns disease, pernicious anemia, Gastrectomy , Fish Tapeworm ◦ Diphyllobothrium latum Signs and Symptoms -Glossitis (beefy tongue), other GI c/o (anorexia, diarrhea) -Pale, icteric -Complex Neurologic syndrome: ◦ Paresthesias impaired sensation to deep touch, pressure and vibration. ◦ Ataxia / Balance difficulties ◦ Decreased or absent DTR's ◦ Pathologic reflexes (ie Babinski in adult) Lab Findings: -Moderate to severe anemia -MCV usually very high (110 - 140 fL) -Peripheral blood smear: Anisocytosis , poikilocytosis, macro-ovalocyte (characteristic of this), hypersegmented neutrophils -Reticulocyte count is down Can see pancytopenia if severe -BM: Marked erythroid hyperplasia, megaloblastic changes, -Elevated LDH and slight increase in indirect bili. (d/t intramedullary destruction) ' -Abnormally low serum B12 ◦ Normal >240 pg/mL ◦ Borderline B12 deficiency 170-240 ◦ Symptomatic <100 ◦ B12 level is how you discriminate b/w myelodysplasia, folic acid deficiency and B12 deficiency Treatment -Parenteral Cobalamin: ◦ IM 100mcg daily for first week ◦ Weekly for the first month ◦ Monthly for life ◦ Can use oral but significantly less absorbed ◦ 100-250 mcg/day for life Brisk Reticulocytosis in first week -Hematologic picture normalizes in 2 months --Neuro symptoms may reverse if treatment started within 6 months. May be permanent if Tx was delayed.

Acute Kidney Injury (aka ARF)

Definition: Abrupt fall in GFR over a period of minutes to days with rapid & sustained rise in nitrogenous waste products in blood. Rate of production of metabolic waste exceeds the rate of renal excretion Classification according to severity and outcome Multiple etiologies GFR & Serum creatinine: Serum creatinine poor marker of renal function. Poor correlation between Serum Creatinine and level of GFR related to muscle mass. Serum Creatinine of 1.0 does not represent the same level of GFR in a cachectic 70-yearold as in a highly muscular 25-year-old. Recent studies suggest that even small increases in SCr increase risk of death 10,000 inpatients: increase in SCr of 0.3 or 0.4 mg/dL leads to 70% higher adjusted odds of death in hospital Following CABG: 50% to 99% increase in SCr leads to 6.6-fold higher adjusted risk of death at 90days Life threatening consequences: Volume overload Hyperkalaemia Uremia: Pericarditis Encephalopathy Platelet dysfunction Metabolic acidosis Management: Identify and correct pre-renal and post-renal factors Optimise cardiac output and RBF- Review drugs: -Stop ACEI, ARBs, NSAIDs -Adjust doses / monitor drug concentrations (where appropriate) Accurately monitor fluid balance and daily body weight Identify and treat acute complications: -Hyperkalaemia, -Acidosis, -Pulmonary edema Prevention: Avoid nephrotoxins: Aminoglycosides: 33 % of nephrotoxicity "therapeutic levels" Amphotericin hydration, Liposomal formulation Radiocontrast media: Hydration N-acetyl cysteine Labs: Elevated BUN/Cr Electrolytes/ECG findings: Hyperkalemia: PeakedT waves‐ PR prolongation wide QRS Hypocalcemia: long QT Hyperphosphatemia Anion gap acidosis

Chronic Kidney Disease

Definition: National Kidney Foundation (NKF) defines CKD as evidence of renal damage based on abnormal UA [proteinuria, hematuria] -or‐ Structural abnormalities found w renal ultrasound orGFR < 60 mL/min for 3 or more months Overview: Symptoms develop slowly and are nonspecific Pts may remain asymptomatic until renal failure is far ‐advanced (GFR < 10 ‐15 ml/min) Manifestations can include fatigue, malaise, weakness, pruritis GI symptoms: c/o anorexia, n/v, metallic taste and hiccups are common Affects up to 20 millionAmericans, 1 of 9 adults Many unaware ‐ asymptomatic until significant progression of the disease National Kidney Foundation's staging system helps clinicians formulate practice plans Over 70% of cases of late‐stage (stage 5) CKD d/t DM or HTN Glomerulonephritis, cystic diseases, and other urologic diseases account for 12%, 15% of patients have other or unknown causes. Progressive azotemia over months to years. Symptoms and signs of uremia when nearing end‐stage disease. Hypertension in the majority. casts in urinary sediment common Bilateral small kidneys on ultrasound are diagnostic. Clinical Findings: PE reveals a chronically ill‐appearing pt Look for possible underlying cause (DM, lupus) HTN is common Skin may be yellow, with evidence of easy bruising Uremic fetor (fishy breath) may be present Cardiopulmonary and mental status changes frequently noted Labs Dx made by documenting elevations of BUN and serum creatinine concentrations GFR...once < 60, refer to Nephrologist Persistent proteinuria is suggestive of CKD, regardless of GFR level UA: broad, waxy casts (evidence of loss of tubular concentrating ability) May see anemia, metabolic acidosis, hyperphosphatemia, hypocalcemia, and hyperkalemia...with both acute and chronic renal failure Further eval needed to differentiate between acute and chronic renal failure Evidence of previously elevated BUN and creatinine, abnormal priorUA, and stable but abnormal serum creatinine on successive days is most consistent w/ chronic process Complications (of uremia): Hyperkalemia Acid‐base d/o Cardiovascular Hematologic Neurologic Disorders of mineral metabolism Endocrine d/o Tx ACE/ARB to slow progression of proteinuria and CVD Maintain excellent diabetes control...keep HgA1C < 7 Tx: early consultation: nephrology, vascular, general surgery Tx (Dietary) - Every pt should be eval by renal nutritionist -Protein restriction: generally, protein intake < 1 g/kg/d - Salt and water restriction: For the nondialysis pt approaching ESRD, 2 g/d of sodium is initial recommendation Potassium restriction: OnceGFR has fallen below 10‐20 mL/min, potassium intake limited to < 60‐70 mEq/d Phosphorus restriction: - Phosphorus level should be < 4.6 mg/dL - Phosphorus binders required ifGFR < 20‐30 mL/min Magnesium restriction: No magnesium‐containing laxatives or antacids When to Refer Patients w/ stage 3-5 chronic kidney disease should be referred to a nephrologist for management of chronic kidney disease in conjunction with the primary care provider. A patient w/ other forms of CKD should have an initial visit w/ nephrologist to discuss future co ‐management needs. When toAdmit Admission should be considered for pts w/ decompensation of problems related to CKD such as worsening of acid ‐base status, electrolyte abnormalities, volume status that cannot be appropriately treated in the outpatient setting. Admission is appropriate when a pt needs to start renal replacement therapy, and is not stable for outpatient initiation. Screening: Screening tests for CKD in high risk groups not well studied‐ recommendations opinion based Hx DM, CVD, HTN, HLD, obesity, metabolic syndrome, smoking, HIV or HCV infection, and malignancy Family history of kidney disease Treatment with potentially nephrotoxic drugs Those w/ family history of CKD should be tested Q 3 yrs Screening of diabetic patients at least annually Due to relatively low prevalence of CKD in theU.S.‐ massive screening of general population not recommended

Anemia

Definition: ■ Absolute decrease in RBC's in proportion to the total blood volume ■ an absolute decrease in hemoglobin (HGB) with respect to blood volume ■ Hct : Women - <37% ■ Men - < 41% ■ Exceptions: - Athletes - High altitude - Smokers - African-Americans ( 0.5-1.0 g/dL below 'norm') - Chronic disease Mechanisms 1. Inadequate production of erythrocytes: ■ Altered HGB synthesis - Iron deficiency anemia - Thalassemia - Anemia of chronic disease ■ Altered DNA synthesis resulting from deficient nutrients - Vitamin B12 deficiency - Folate deficiency ■ Bone marrow infiltration - Cancer - lymphoma 2. Excessive destruction of erythrocyte ■ Hereditary hemolysis - Sickle cell trait or disease ■ Acquired hemolysis - Immune mechanisms (blood transfusion reaction) - Infection (Malaria, clostidial) - Drugs (quinidine, penicillin, methyldopa) - Liver or kidney disease - Toxins (chemical, venoms) 3. Blood loss ■ Acute - Hemorrhage, trauma ■ Chronic - Gastrointestinal bleeding - Menorrhagia Classification ■ Morphologic: - *Cellular erythrocyte size and Hgb content - MCV, MCHC - Microcytic, Macrocytic, Normocytic ■ Kinetic - Pathophysiologic cause for fall in RBC count - Decrease erythrocyte production - Increased erythrocyte destruction - Blood loss Physical Exam ■ Laboratory Studies - CBC: ■ Hgb: Males: 13.5-17 grams/dl Females: 12- 15.5 Gm/dl ■ Hct: Males: 41% - 50% Females: 35% - 46 % ■ RDW: < 15% ■ MCV: 78 - 100 femtoliter - Normocytic, Microcytic, Macrocytic, ■ MCHC: 32-34 gm/dl ■ MCH: 27-34 - Hypochromic ■ Reticulocytes: new RBC

• Factor Xa inhibitors

Directly inhibit factor Xa by preventing factor Xa from cleaving prothrombin to thrombin o Inhibit circulating and clot bound factor Xa • No parenteral formulations • Oral agents: 'xaban' o Rivaroxaban (Xarelto) o Apixaban (Eliquis) o Edoxaban (Lixiana, Savaysa) o Betrixaban (Bevyxxa) • Metabolized in kidney and liver o Liver impairment results in accumulation of agent. Limited data in obese patients - generally avoided • Fondaparinux (Arixtra) - • Anticoagulant, Factor Xa inhibitor.... • indirectly inhibits factor Xa as heparins do via AT, but it does not inhibit thrombin at all. o Longer T ½ than heparin o Does not bind to platelets - does not cause HIT o 5-10 mg SQ QD for Tx, Prophylaxis: 2.5 mg daily SQ o After Sub Q admin - 100% bioavailable, peaks in 25min to 1.5hrs, T1/2 15- 17+ hours - anticoag activity persists for 3-5 T1/2 after D/C o Significant renal clearance, not recommended if CC<30mL/min o No specific antidote or reversal agent

Renal Artery Stenosis (chronic RVD)

Essentials of Diagnosis Produced by atherosclerotic occlusive disease (80-90% of patients) or fibromuscular dysplasia (10-15%) Hypertension Acute kidney injury in patients starting therapy with anACE inhibitor. General Considerations Atherosclerotic ischemic renal disease accounts for nearly all cases of renal artery stenosis Most common > 45 years of age w/ history of atherosclerotic disease Other risk factors include: chronic kidney disease, diabetes mellitus, tobacco use, HTN Signs/Symptoms refractory hypertension new‐onset hypertension In an older adult physical exam may reveal an audible abdominal bruit on the affected side Fibromuscular dysplasia primarily affects young women. Unexplained hypertension in a young woman is reason to screen for this disorder Laboratory Findings: can show elevated BUN and serum creatinine levels in the setting of significant renal ischemia Imaging: Abdominal ultrasound can reveal asymmetric kidney size when one renal artery is affected out of proportion to the other Three common methods used for screening: Doppler ultrasonography, CT angiography, and magnetic resonance angiography (MRA) Renal angiography is the gold standard for diagnosis Treatment Options: medical management, angioplasty w/ or w/o stenting, and surgical bypass Angioplasty may reduce the number of antihypertensive medications but does not significantly change outcome in comparison to patients medically managed Stenting produces significantly better angioplastic results; However, blood pressure is equally improved, and serum creatinines are similar at 6 months of observation compared with both angioplasty and stents. Angioplasty is equally as effective as, and safer than, surgical revision

Anticoag risks

Estimating Thromboembolic risk • Greatest risk from o Atrial Fibrillation • Heterogeneous group • Tools to predict eg. CHA2DS2-VASc score o Prosthetic heart valves o Recent venous or arterial thromboembolism (w/in 3 months) • If Sx or procedure can be delayed, the risk reduces significantly after 3 months without an event Estimating Bleeding Risk • Considerations o type of procedure: high risk -vs- low risk • High risk: CABG, Kidney biopsy, longer than 45 minutes • Low risk: cholecystectomy, carpal tunnel release, abdominal hysterectomy • Neuraxial, intracranial, and cardiac procedures are of particular concern/ risk • Cardiac implantable device OR catheter ablation for A Fib - continuing warfarin is associated with a lower risk of bleeding in the BRUISE CONTROL trial and the COMPARE trial o Patient comorbidities o Medications

Macrocytic Megaloblastic Anemia: Folic Acid deficiency

Folic acid found in most fruits and vegetables ◦ Particularly citrus fruits and green leafy vegs Absorbed through entire length of GI tract Daily requirement : 50-100mcg Body stores are about 5000 mcg ◦ 2-3 month requirement -Most common cause of deficiency: DIET ◦ Alcoholics, eating disorders, overcooked food, diets that exclude fruit/veg Signs and Symptoms -Similar to B12 deficiency minus neurologic -GI: beefy tongue/glossitis, anorexia, diarrhea -Pale, icteric Lab findings: -Moderate to severe anemia -MCV usually very high (110 - 140 fL) -Peripheral blood smear: Anisocytosis , poikilocytosis, macro-ovalocyte (characteristic of this), hypersegmented neutrophils -Reticulocyte count is down -Can see pancytopenia if severe BM: Marked erythroid hyperplasia, megaloblastic changes, -Elevated LDH and slight increase in indirect bili. (d/t intramedullary destruction) -Abnormally low serum -Folic Acid: <150 ng/mL Serum B12 is normal

Glomular filtration rate

GFR provides a useful index of overall kidney function Useful for staging CKD Pts w/ kidney disease can have normal or increasedGFR GFR measures the amount of plasma ultrafiltered across the glomerular capillaries Correlates w/ the ability of the kidneys to filter fluids and various substances Daily GFR is normally variable: -with a range of 150-250 L/24 h ‐or -100-120 mL/min/1.73 m2 of body surface area Estimation ofGFR gives an approx. measure of the number of functioning nephrons

Red blood cell cast

Glomerulonehpritis

Normocytic Anemia: Sideroblastic Anemia

Hbg synthesis reduced d/t failure to incorporate heme. ◦ Intracellular iron accumulates ◦ Typically acquired, subtype of myelodysplasia ◦ Can be d/t ETOH abuse, lead poisoning Clinical features r/t anemia (moderate- HCT 20-30%) ◦ MCV usually normal, can be increased or decreased ◦ Serum iron is elevated ◦ Transferrin saturation is high ◦ Peripheral blood smear dimorphic RBC's ◦ Lead poisoning - basophilic stippling, serum lead increased Dx by BM: ◦ Marked erythroid hyperplasia, increase in iron stores, ringed sideroblasts

CKD complications

Hyperkalemia K+ balance usually intact until GFR < 10 ‐20 mL/min Tx of acute hyperkalemia: cardiac monitoring, IV calcium chloride or gluconate, insulin with glucose, bicarbonate, and sodium polystyrene sulfonate Chronic hyperkalemia tx'd with dietary potassium restriction, and sodium polystyrene PRN Acid‐base disorders Damaged kidneys are unable to excrete the acid generated by metabolism of dietary proteins Metabolic acidosis results primarily due to loss of renal mass Treatment: Maintain serum bicarb level at > 21 mEq/L Alkali supplements include sodium bicarbonate, calcium bicarbonate, and sodium citrate Cardiovascular complications HTN is most common complication of ESRD HTN control w/ weight loss and tobacco cessation Salt intake reduced to 2g/day Initial RX to includeACE I or ARB If serum potassium andGFR permit (recheck 1 wk) Goal BP is <130/80 mm Hg → w/ proteinuria > 1‐2 g/d, goal is < 125/75 mm Hg Cardiovascular complications (pericarditis) Pericarditis may develop with uremia Cause believed to be retention of metabolic toxins Symptoms include CP and fever May have pulsus paradoxus and friction rub on exam Pericarditis is an absolute indication for initiation of hemodialysis Cardiovascular complications (CHF) Pts w/ ESRD trend toward a high cardiac output, extracellular fluid overload, anemia In addition to HTN, causes increased myocardial work and oxygen demand Increased rate of atherosclerosis All of the above contributes to LVH and dilation present in 75% of pts starting dialysis Tx w/ loop diuretics, ACE I, and regulation of salt and water Hematologic complications: Anemia:Normochromic, normocytic Relative deficiency of erythropoietin Diminished red blood cell survival Iron deficiency Hyperparathyroidism/bone marrow fibrosis "Chronic inflammation" Folate or vitamin B12 deficiency Hemoglobinopathy Comorbid conditions: hypo/hyperthyroidism, pregnancy, HIV‐ associated disease, autoimmune disease, immunosuppressive drugs Recombinant erythropoietin (epoetin alfa) used in pts whose hematocrits are < 33% Iron supplement PRN Hematologic complications: Coagulopathy: Mainly platelet dysfunction Platelets mildly decreased Prolonged bleeding time Platelets show abnormal adhesiveness and aggregation Pts may present with petechiae, purpura, and increased bleeding during surgery Dialysis improves bleeding time but doesn't normalize it Tx goal = Hct increased to 30% Neurologic complications Uremic encephalopathy ‐not untilGFR falls below 10‐15 mL/min Begins w/ difficulty in concentrating and can progress to lethargy, confusion, and coma Neuropathy found in 65% of pts on or nearing dialysis but not untilGFR is 10% of normal Earlier initiation of dialysis may prevent peripheral neuropathies Neurologic problems include irritability, difficulty concentrating, insomnia, and forgetfulness Menstrual irregularities, infertility, loss of libido Disorders of mineral metabolism Disorder of calcium, phosphorus, and bone are referred to as renal osteodystrophy Most common ‐ osteitis fibrosa cystica - the bony changes of secondary hyperparathyroidism...affecting 50% of pts nearing ESRD Radiographically, lesions most prominent in phalanges and lateral ends of clavicles Disorders of mineral metabolism May also have osteomalacia Can cause bony pain, proximal muscle weakness, and spontaneous bone fractures Tx : dietary phosphorus restriction, oral phosphorus ‐ binding agents such as calcium carbonate or Renogel, and vitamin D Hyperparathyroidism :tx w/ calcitriol or Sensipar Endocrine disorders Circulating insulin levels are higher d/t decreased renal insulin clearance Glucose intolerance can occur in chronic renal failure when GFR is < 10‐20 mL/min mainly due to peripheral insulin resistance Decreased libido and impotence are common Men have decreased testosterone Women are often anovulatory

Cervical Cancer

Impact 12,000 women in US annually § Most common in women > 30 years old § Main cause is HPV 16/18 § At least half of sexually active women will have HPV at some point in their life § Few will go on to develop cervical cancer § Two types of screening test § Cytology: Pap test or Pap smear Used to detect precancers or cell changes on the cervix § Recommended for women between 21 - 65 years old § HPV testing starting at 30. Screening: Age 21-29: Cytology alone every 3 years § HPV testing not recommended (not as co test or stand alone) Age 30 - 64: Cytology and HPV (CoTesting) every 5 years preferred § Cytology alone every 3 years is acceptable Cotest: HPV + and cytology Negative: One of the following: -Repeat cotest in 12 months - or- - Immediate HPV genotype for HPV 16/18; refer to colposcopy isn't indicated. If positive for either HPV 16/18 refer for colposcopy § If repeat Cotest is positive - refer for colposcopy § If repeat CoTest is negative - return to normal screening Prevention: Gardasil, Cervarix for HPV genotypes 16/18 Common s/s: Metrorrhagia, postcoital spotting, cervical ulceration Staging: Biopsy, Imaging then use TNM system Treatment: § In situ: hysterectomy, or to retain possible childbearing potential ablation via cryotherapy/laser or cervical conization § Surgery § Chemotherapy § Radiation therapy

Von Willebrand Disease (vWD)

Most common inherited bleeding disorder • Estimated to affect 1% of population • Type 1 (75-80%) , Type 2 (15 - 20%) - vWF bridge platelets together and tethers them to the sub endothelial matrix. Also prolongs the ½ life of Factor VIII - Platelet -type bleeding - Nosebleeds, bruising, bleeding gums - mucous membranes, skin - Joint bleeding rare (vs hemophilia's) • Testing: bleeding time, Factor VIII level, von Willebrand antigen, Ristocetin cofactor activity (binds vWF to platelets) • TX: DDAVP, cryoprecipitate,

Prostate Cancer

Most common non cutaneous cancer in men in US § 2nd cause of male cancer related death § Found on autopsy in 2/3 of men 80-89 y/o § Average lifetime risk is 40% § Risk Factors: - Age - African American ancestry - Family history of prostate cancer - obesity Screening: § Most cases asymptomatic § DRE: -Good for screening posterior lobe -Somewhat clinician subjective -Can reveal painless area of induration - often advanced § PSA: -Specific to prostate epithelium not prostate cancer: PBH, infection, infarction, trauma, manipulation can increase PSA Normal values: § <4 ng/ml normal range § < 2.5 ng/ml - recheck in 2 years; if > 2.5 ng/ml check yearly § Age adjusted! § PSA velocity / doubling time § About 25% of men b/w 4-10 ng/ml will have cancer § Nearly 2/3 of men >10ng/ml will have cancer § Start screening discussion at 50 y/o if life expectancy > 10 yrs § High risk groups 40-45 y/o Staging: Gleason Ie (3+4) Treatment: § Organ confined: Active surveillance § Surgery: Radical prostatectomy OR Nerve sparring robotic prostatectomy- Da Vinci prostatectomy § Radiation:External beam, Brachytherapy, or Both Hormone driven: Testosterone § Hormone ablation- Androgen Deprivation Therapy w. Luteinizing hormone-releasing hormone agonists - leuprolide/Lupron, goserelin/Zoladex: hypothalamic - pituitary axis, eliminates 90-95% of testosterone. Castrate level in 10-14 days. § Addition of Casodex /bicalutamide to prevent flare of PSA with start of Tx? § AntiAndrogens: flutamide, bicalutamide, enzalutamide, nilutamide § Hormone refractory (median survival 36 months) Metastasizes to: Surrounding tissue (lymphatics, vascular, perineural channels). then to Bone

Requirements or normal renal function

Normal renal blood flow Functioning glomeruli and tubules Clear urinary outflow tract for drainage and elimination of formed urine

Oliguria, Anuria, and Nonoliguric values

Oliguria ‐ < 400 mL/24 h Anuria ‐ < 100 mL/24 h Nonoliguric ARF ‐ > 400 ml / 24 h

AKI: Postrenal Azotemia

Overview Also referred to as "obstructive" Urine flow obstructed Elevated intraluminal pressure in ureter - urine reflux into renal pelvis and parenchyma Decreased renal blood flow and renal tubule function decrease inGFR Least common cause ofAKI 5‐10% of cases Early detection = uncomplicated reversal Causes: Urethral obstruction: can be constant or intermittent, partial or complete Bladder dysfunction or obstruction Obstruction of ureters or renal pelvises •BPH in men •Neoplasm •Retroperitoneal •Neurogenic bladder •Anticholinergic drugs •Less common causes: •Blood clot •Bilateral ureteral stones •Urethral stone or stricture Signs and symptoms: May or may not be anuric c/o lower abd pain Physical exam findings: BPH Distended bladder Mass on pelvic exam Lab findings: similar to prerenal d/t lack of intrinsic damage

DVT

Predisposing Factors: • Age, 60 and older • Large bone fracture: Hip, Femur • Recent surgery • Immobility and/or Obesity • Pregnancy • Meds • Smoking • Cancer • Inherited hypercoagulable conditions • Assessing risk: Padua Risk Assessment Model (refer to Current Medical Diagnosis and Treatment ) • Symptoms: Sudden, unilateral • Extremity pain - edema • Increased temperature of extremity • Change in color of extremity • Some are asymptomatic depending on location • Potential Complication: • PE • Arterial embolism with AV shunting • MI • CVI • Postphlebetic syndrome • Subjective Data • When symptoms began • Duration • Type of pain • Alleviating, aggravating factors • Pain intensity • Medications, drugs, supplements • Recent procedures, surgeries • PE • Vitals • Inspect area • Homans sign? Moses' sign? • Lisker sign? • Palpate: pulses distal, cap refill, tenderness NO deep palpation • Auscultate: heart/lungs • Diagnostics • Labs: CBC, D-Dimer, Coagulation Panel • Idiopathic DVT: Factor V Leiden, Homocysteine, G20210A Prothrombin, Factor VIII, lupus anticoagulation, Protein C&S anticardiolipin antibodies, antithrombin • Compression US • MRI • Venography (not routinely used) Treatment • Non pharmacologic: compression hose etc. • Selection of Anticoagulant based on Patient conditions (kidney Fxn, bleeding risk, weight) and clinical scenario • Length of treatment: • Major / Minor transient risk factor: 3 months • Cancer related: 3-6 months or as long as cancer is active -which ever is longer • Unprovoked thrombus: at least 3 months, consider indefinite • Thrombophilia: indefinite • The Vienna Prediction Model • Normal D-Dimer at 1 month after DC-ing meds associated with lower recurrence • Men 2x more risk for recurrence • PE more likely to recur if 1st PE was clinically apparent versus those with DVT alone • Follow Up • Determined by needs • Cardiologist and/or anticoagulant clinic

Thrombin Inhibitors

Prevent thrombin from cleaving fibrinogen to fibrin - bind directly to thrombin (not AT like heparin) • Parenteral: o Bivalirudin (Angiomax), argatroban (Argatra, Novastan, Arganova, Exembol), desirudin (Iprivask, Revasc) • Oral: o Dabigatran etexilate (Pradaxa)

Major causes of CKD

Primary glomerular diseases: Focal and segmental glomerulosclerosis Membranoproliferative glomerulonephritis IgA nephropathy Membranous nephropathy Secondary glomerular diseases: Diabetic nephropathy Amyloidosis Postinfectious glomerulonephritis HIV‐associated nephropathy Collagen‐vascular diseases Sickle cell nephropathy HIV‐associated membranoproliferative glomerulonephritis Vascular diseases Hypertensive nephrosclerosis Renal artery stenosis Tubulointerstitial nephritis Drug hypersensitivity Heavy metals Analgesic nephropathy Reflux/chronic pyelonephritis Idiopathic Hereditary diseases Polycystic kidney disease Medullary cystic disease Alport syndrome Obstructive nephropathies Prostatic disease Nephrolithiasis Retroperitoneal fibrosis/tumor Congenital

Macrocytic anemias

RBC's are large, often insufficient amount, insufficient Hgb content Types: ◦ Megaloblastic anemias: Folate, B12 deficiency, poisons, some antiviral drugs and some chemo agents ◦ Red cell membrane disorder producing codocytes (target cells):Pathologies of liver and spleen ◦ Alcohol:

Breast Cancer

Screening: § Shared decision making § Mammogram annually after 40 § Every one to two years § Beyond 75 y/o question whether to continue screening LCIS Lobular Carcinoma in Situ § Thought that this isn't a true malignancy but an indicator of increased risk § Follow closely & Monthly BSE § Clinical breast exam every 6 months § Breast Cancer Prevention Trial: Tamoxifen for 5 years decrease invasive cancer by 50% DCIS Ductal Carcinoma in Situ. § Malignancy within the ductal system & Can progress to invasive. § Invasive DCIS- - most commonly diagnosed invasive breast cancer - Moves from the mild ducts into surrounding tissues § Lymph nodes rarely involved in DCIS (non invasive) § Tx: Lumpectomy: assess for Clear margins Chemotherapy? § Adjuvant - vs- neo adjuvant § Onco type DX § HER-2/neu oncogene: Herceptin §Radiation? Determined by Tumor size, invasive, nodal involvement, + margin §Estrogen receptors/ Progesterone receptors (hormonal therapy): Tamoxifen, aromatase inhibitor Inflammatory Breast Cancer: Neo-adjuvant Chemotherapy(early chemo) § Very aggressive malignancy § If response to chemo: - Surgical resection - Radiation therapy § Follow up § Regular exams ipsilateral and contralateral § First 2 years Q 6 months then annually § If it recurs, Most likely to recur in the first 2 - 5 year TNM staging: § Stage at diagnosis most reliable prognosticator (N) Example of TNM staging § Tx - Primary tumor is unable to be assessed. § T0 - No evidence of primary tumor. § Tis - Carcinoma in situ. § •Tis (DCIS) - Ductal carcinoma in situ. § •Tis (Paget) - Paget disease of the nipple not associated with invasive carcinoma and/or DCIS in the underlying breast parenchyma. Carcinoma in the breast parenchyma associated with Paget disease is categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted. § T1 - Tumor ≤20 mm in greatest dimension. § T1mi - Tumor ≤1 mm in greatest dimension. § T1a - Tumor >1 mm but ≤5 mm in greatest dimension (round any measurement 1.0 to 1.9 mm to 2 mm). § •T1b - Tumor >5 mm but ≤10 mm in greatest dimension. § •T1c - Tumor >10 mm but ≤20 mm in greatest dimension. § T2 - Tumor >20 mm but ≤50 mm in greatest dimension.

Carcinogenesis

Stages -Transformation -Growth -Local invasion -Metastasis Necessities for malignancy -Self sufficiency in growth signaling Insensitivity to anti-growth signals -Evading apoptosis -Immortalization -Sustained angiogenesis -Tissue invasion and metastasis Oncogenes & Tumor Suppressor Genes Oncogene: positive regulator of growth. Normal cellular genes that when altered can induce malignant transformation. Tumor Suppressor Gene: negative regulators: Gene products (proteins) capable of controlling expression of proto-oncogenes to oncogenes Carcinogens -Radiation -Sun, ionizing -Infectious agents -Virus, bacteria, flatworms -Chemical compounds -Vinyl chloride -Foreign body reactions -Asbestos, silica, tobacco **Tobacco Those who smoke before 15y/o are twice as likely to develop a lung Ca as those who start after 20y/o. 90% of lung cancers are due to tobacco (3-5% from secondary smoke). Immunosuppression and cancer -Immune surveillance is the primary host defense against carcinogenesis -In the presence of immunosuppression cancer may grow very quickly -AIDS Autoimmune disease treatment -Transplant patients Grading G1 - well differentiated G2 - moderately differentiated G3 - poorly differentiated G4 - undifferentiated anaplastic Mitotic index : the percentage of tumor cells that are actively dividing Staging TNM classification T = Tumor N = Nodal involvement M = Metastasis (at time of diagnosis) Eg. Breast cancer T1bN0Mx

FXaI: Betrixaban (Bevyxxa)

T1/2 = 19 to 27 hrs • Indication: o Prevention of VTE in hospitalized adult medical patients and acutely ill • Do not use in pregnancy or patients with prosthetic heart valves • Dosing o Fixed dose without monitoring • Typical dose is 160 mg first day then 80 mg once daily • Doses same time daily and with food • Reduce by half if CC<30 mL/min or using P-glycoprotein inhibitors • Black Box Warning with neuraxial anesthesia

1) Beta thalassemia minor is considered a:

a) Macrocytic anemia b) Normocytic anemia c) Microcytic anemia d) Hemolytic anemia

1) The red blood cells in pernicious anemia will show:

a) Microcytic cells b) Hyperchromic cells c) Macrocytic cells d) Hemolytic cells

Presenta6on • Sally is a 62 y/o female with a 12 year history of diabetes type 2 and HTN. She is here for an ini6al visit to establish care in your office practice. • She reports no troublesome symptoms except for some ankle edema. • She does not exercise and is a life6me nonsmoker. Medications • Sally is on the following medicatons: - Amlodipine 5 mg daily - Metormin 1000 mg bid - Glargine insulin 12 units at bedtme Physical Examina6on • T- 98.2, P- 84, R-18, BP- 152/90 • Cardiac: S1S2, RRR, no M/R/G • Lungs: CTA • ABD: SoW, nontender, nondistended normoac6ve bowel sounds • Extremities: trace pre6bial edema bilaterally • (the NP would perform a more extensive exam including a monofilament test on the patient's feet, but that is not relevant to our case) Question 1 • What else do you want to know about this pa6ent and what is your opinion of her BP? Answer Ques6on 1 • Nurse Practitioner Thoughts...... • The goal for BP control in a diabe6c pa6ent is <130/80, so this pa6ent is clearly not op6mally controlled • How about a renal panel (BMP)? • How about a urinalysis? • When was this pa6ent's last eye exam? • What other lab work might you want to order? Here is your data..... • Urinalysis: - positive for protein: 350mg/d, no RBCs, no RBC casts. • Renal panel: - normal except for serum creatinine 1.8 • Hemoglobin A1C: 8.2 • They are scheduled with ophthalmology for a comprehensive eye exam • You are considering your op6ons for BP management......

What is the most appropriate next step in the management of this pa6ent? • A. add lisinopril 5 mg daily • B. refer for a renal biopsy • C. refer for a renal ultrasound • D. add metoprolol Answer Ques6on 3 • You ini6ated lisinopril and your pa6ent returns in 2 weeks for follow-up. Today her BP is 144/86 and her serum crea6nine is 2.0. • What is the most appropriate next step in the management of this pa6ent? • A. discon6nue lisinopril • B. add losartan • C. increase the dose of lisinopril • D. schedule a renal biopsy Rationale for Questions 2 & 3 • Uncontrolled HTN and proteinuria are important modifiable risk factors for progressive kidney disease in this diabe6c pa6ent. BP goal is <130/80 or < 125/75 in Pts w/ significant proteinuria. • ACE inhibitors and ARBs are the preferred agents to slow the progression of chronic kidney disease. • Remember, ACEI/ARBs reduce efferent arteriolar resistance and lowers intraglomerular pressure; which may result in decreased GFR and slightly increased serum crea6nine. An increase in serum crea6nine of up to 30% is acceptable. It is not necessary to discon6nue the lisinopril. • You would not add an ARB to an ACEI. The data suggests no benefit in morbidity and mortality and increased risk of adverse drug effects when these agents are combined. • The pa6ent could be referred to nephrology if you were not comfortable, but a renal biopsy would not be indicated

Hemophilia

X linked recessive • Hemophilia A (VIII): 1 in 5000 males: 25% develop inhibitor to F VIII. • Hemophilia B (IX) : 1 in 25,000 males:5% develop inhibitor to F IX • Severe cases: • Presents in infancy or very early childhood • Spontaneous bleeding into joints/soft tissues • Mild cases: • Spontaneous bleeding is rare • Bleeding may occur with significant challenge to hemostasis • Hemophilic arthropathy • Side effect of bleeding into joint spaces • Can be avoided or blunted if Factors are given in childhood • Common in adults with hemophilia • Pain • Immobilization • Severe arthritis • Labs: low factor VIII or IX • Classified according to factor activity in plasma • Severe: <1% factor activity • Moderate: 1-5% • Mild: >5% • Treatment: DDAVP, plasma derived or recombinant factors • Severe: by age 4 • Long term prophylactic 2 to 3 times/week (infusions) • Adults typically PRN • Mild: Often respond well to IV or intranasal DDAVP prn • COX-2 inhibitors for pain • Oral opioids for pain/surgery • Joint replacement • Outpatient procedures may be made inpatient

1) Which of the following individuals is more likely to be affected by alpha thalassemia anemia?

a) 53 year old Greek patient b) 25 year old Chinese patient c) 62 year old Russian patient d) 38 year old African American patient

1) Which of the following is the most likely candidate to initiate dialysis due to chronic kidney disease?

a) A 46 year old man with hypertension and GFR = 42 ML/min b) A 64 year old woman with type 2 diabetes and GFR = 28 ML/min c) A 76 year old man with anemia and GFR = 55 ML/min d) A 58 year old woman with heart disease and GFR = 46 ML/min

1) Current limitations of screening smokers with CT scan include all of the following except:

a) A high false positive rate b) Low sensitivity c) Radiation exposure from multiple CT scans d) Patient anxiety

1) All of the following are common precipitating factors in acute renal failure except:

a) Anaphylaxis b) Infection c) Myocardial infarction d) Type 1 diabetes

1) Which part of the prostate is readily palpable during a DRE?

a) Anterior lobe b) Median lobe c) Lateral lobes d) Posterior lobe

1) The most common cause of cancer deaths for women in the US is:

a) Breast cancer b) Lung cancer c) Colon cancer d) Uterine cancer

1) Pernicious anemia causes which of the following changes in RBC indices?

a) Microcytic, normochromic b) Normocytic, normochromic c) Microcytic, hypochromic d) Macrocytic, normochromic

1) A 16 year old female patient is being treated for her first UTI. She had an allergic reaction with hives after taking sulfa as a child.. Which of the following antibiotics would be contraindicated?

a) Cephalexin (Keflex) b) Amipicillin (Amoxil) c) Trimethoprim-sulfamethoxazole (Bactrim) d) Nitrofurantoin crystals (Macrobid)

1) Typical symptoms of lung cancer caused by a primary tumor include all of the following except:

a) Chest discomfort b) Dyspnea c) Hoarseness d) Hemoptysis

1) A new patient is being interviewed. She reports that she had a gastrectomy procedure 5 years ago to treat severe obesity. Currently, her body mass index is 25 and the patient denies complications from the procedure. The nurse practitioner is aware that the patient is at higher risk for which of the following disorders?

a) Folate deficiency anemia b) B12 deficiency anemia c) Iron deficiency anemia d) Normocytic anemia

1) Which of the following human papillomavirus (HPV) strains is associated with cervical cancer?

a) HPV subtypes 12 and 14 b) HPV subtypes 16 and 18 c) HPV subtypes 20 and 26 d) HPV subtype 30

1) Which of the following tests would you recommend to patients to confirm the diagnosis of sickle cell anemia?

a) Hemoglobin electrophoresis b) Bone marrow biopsy c) Peripheral smear d) Reticulocyte count

1) All of the following electrolyte disorders are commonly found in a person with chronic renal failure except:

a) Hypernatremia b) Hypocalcemia c) Hyperkalemia d) Hypophosphatemia

What is the name of the immune process that is responsible for anaphylactic reactions

a) IgE mediated reaction b) IgG mediated reaction c) Antibody reaction d) Atopic reaction

1) Angiotensin converting enzyme inhibitors can limit the progression of some forms of renal disease by:

a) Increasing intraglomerular pressure b) Reducing efferent arteriolar resistance c) Enhancing afferent arteriolar tone d) Increasing urinary protein excretion

1) A 35 year old patient is being worked up for microscopic hematuria. All of the following are differential diagnoses of microscopic hematuria except:

a) Kidney stones b) Bladder cancer c) Acute pyelonephritis d) Renal artery stenosis

1) Which of the following is most consistent with iron deficiency anemia?

a) Low MCV, normal MCH b) Low MCV, Low MCH c) Low MCV, elevated MCH d) Normal MCV, normal MCH

1) Erythropoietin is a glycoprotein that influences a stem cell to become a:

a) Lymphocyte b) Platelet c) Neutrophil d) Red blood cell

1) In the US, the most common cause of cancer deaths in men is:

a) lung cancer b) prostate cancer c) colon cancer d) skin cancer

Anticoagulants

o Anticoagulants • Heparin o Unfractionated o LMWH: • Lovenox (enoxaparin sodium) • Fragmin (dalteparin sodium) • Vitamin K Antagonists: o Coumadin (warfarin) • Factor Xa inhibitors o Indirect: Arixtra (fondaparinux sodium) o Direct: 'xaban's" : rivaroxaban, apixaban, edoxaban, betrixaan • Direct Thrombin Inhibitors o Dabigatran(PO), parenteral: bivalirudin, argatroban, desirudin

esophageal cancer

§ Usually develops between 50-70 y/o § Men to Women are 3:1 § Two histologic types: Squamous cell § Adenocarcinoma § In US: -Squamous cell more common among Black Americans and 90% in distal 2/3 of esophagus. Chronic alcohol & tobacco use strongly associated with increased risk of squamous cell -Adenocarcinoma more common among White Americans. Incidence increasing - now more common than squamous cell. Majority develop from Barrett metaplasia d/t chronic GERD. Most in the distal 1/3 of esophagus. Obesity strongly associated with increased risk Presentation § Most (50-60%) cases advanced at presentation (incurable) § Early symptoms nonspecific § Eventually progress to § Solid food dysphagia - progressive § Odynophagia § Weight loss § Iron deficient anemia § Coughing upon swallowing suspect tracheo esophageal fistula § Chest or back pain - mediastinal extension § Hoarseness from recurrent laryngeal involvement § Diagnosis and Staging § EGD with biopsy § Trans esophageal ultrasound/biopsy § CT Chest/abdomen § PET scan

esophageal cancer

§ Usually develops between 50-70 y/o § Men to Women are 3:1 § Two histologic types: Squamous cell § Adenocarcinoma § In US: -Squamous cell more common among Black Americans § 90% in distal 2/3 of esophagus § Chronic alcohol & tobacco use strongly associated with increased risk of squamous cell § Adenocarcinoma more common among White Americans § Incidence increasing - now more common than squamous cell § Majority develop from Barrett metaplasia d/t chronic GERD § Most in the distal 1/3 of esophagus § Obesity strongly associated with increased risk

Vitamin K Antagonists

• "Coumarins" o Warfarin, acenocoumarol, phenprocoumon, fluindione • Hepatic production of coagulation factors II, VII, IX,X, and Proteins C & S require Vitamin K - VKA's deplete the Vit K reserves and reduce synthesis of these clotting factors. • Therapeutic range is narrow, dosing can be challenging • Monitored by INR • Steady state can take 5 days • Usually begin on 5 mg • INR weekly initially, no longer than 6 weeks between • Benefits: o Long term use - much clinical data o Low cost, available o Better than other oral anticoag in pt w/ prosthetic heart valves o Reverses with vitamin K, FFP or prothrombin complex concentrates o Can achieve anticoagulant effect in pt with adv renal insufficiency, extremes of weight • Limitations o Higher rates of bleeding/thromboembolic complications in pts with A Fib o Frequent monitoring o Dosing is affected by numerous factors - illness, genetics, diet, medication

Coagulopathy

• Aka: clotting disorder or bleeding disorder • Any condition that can affect the bodies ability to clot • Hypocoagulability vs Prothrombotic • spontaneous or following a procedure • Genetic • Absence of clotting factors • Dysfunction of platelets or thrombocytopenia • Acquired • Drugs( ASA, NSAIDS, Abx, ETOH), Vitamin K deficiency, Liver disease Normal clotting: • Clotting cascade • Begins almost instantly after an injury the endothelium: • Primary hemostasis: platelets form a plug at the site of injury • Secondary hemostasis: simultaneous. Clotting factors respond form fibrin strands which strengthen the platelet plug • Intrinsic pathway / Contact activation pathway • Begins with the formation of the primary complex on collagen • Minor role, those deficient in factors in intrinsic pathway do not develop bleeding disorders...(.more involved in inflammation?) • Extrinsic pathway / Tissue factor pathway • Primary path for initiation of blood coagulation • "Thrombin burst" • Common pathway • Thrombin = Fibrinogen to Fibrin ("building block of hemostatic plug") • Activates Factors VIII and V as well as their inhibitor protein C, also Factor XIII • Prothrombotic state continues as long as Factor VIII and IX are activated, when they are downregulated by anti coagulation pathway the process is stopped

Advantages of DOACs over heparin/warfarin

• Appear to have a lower bleeding risk o Especially intracranial • DOACS generally used without requiring consistent monitoring • Less variable dose response relationship • Not affected by Vitamin K levels • No development of HIT • DTI's inhibit unbound and clot bound thrombin o Important in situations such as percutaneous cardiac interventions

TI: Desirudin (Iprivask, Revasc)

• Dose: o 15 mg Sub Q q 12 hours o First dose 30 minutes before hip arthroplasty or postop • T1/2 o 2 hours: Increased time with renal insufficiency • Black Box warning o Risk of spinal/epidural hematoma w/neuraxial anesthesia

Transitioning Anticoagulants

• Goal: maintain stable anticoagulation • From DOAC to VKA: the full effect of warfarin takes several days despite INR • From VKA to DOAC: resolution of warfarin effect takes several days DOAC to VKA • Dabigatran to warfarin o CC> 50mL/Min: VKA 3 D before d/cing DOAC o CC 30-50 mL/min: VKA 2 D before d/cing DOAC o CC 15-30 mL/min: VKA 1 D before d/cing DOAC • Rivaroxaban or Apixaban to warfarin o Stop DOAC, provide parenteral agent during warfarin initiation • Edoxaban to warfarin o Reduce daily dose by 50% and start warfarin simultaneously - Measure INR at least weekly (prior to daily dose of edoxaban) - o D/c edoxaban when stable INR for 2 days is reached • Betrixaban to warfarin - not determine because only used for VTE prophylaxis VKA to DOAC • Warfarin to: o Argatroban: start argatroban when INR <2.0 o Dabigatran: d/c VKA, monitor PT/INR, start dabigatran when INR <2.0 o Rivaroxaban: d/c VKA, monitor PT/INR, start dabigatran when INR <3.0 o Apixaban: d/c VKA, monitor PT/INR, start dabigatran when INR <2.0 o Edoxaban: d/c VKA, monitor PT/INR, start dabigatran when INR <2.5 • Usually bridge with a LMW heparin - Lovenox • Typically reserved for those with higher risk of thromboembolic event - Embolic stroke/systemic emboli within three months - Mechanical valve - A Fib and high risk of stroke o VTE within three months, recent coronary stenting (12 weeks) - Previous thromboembolism during interrupted anticoagulation • Timing - LMW Heparin bridge - dc 24 hours before procedure o Unfractionated heparin bridge: dc 4-5 hours prior to procedure o Both can be resumed with hemostasis: high bleeding risk restart 48-72 hours after procedure, low bleeding risk restart at 24 hours after • Usually largest challenge is with warfarin • DOAC's have shorter half lives • Still, in any anticoagulated patient consider: o Estimated thromboembolic risk o Estimated bleeding from procedure o Timing of anticoagulation interruption o Is bridging necessary?

Heparin

• Indications and choice of product is situation specific • Clinically used form isolated from porcine or bovine intestine • Unfractionated: Longer polysaccharide chains • Low molecular weight heparins: further derived from unfractionated heparin for smaller/lighter chains • By way of antithrombin (AT), heparins effect Thrombin and Factor Xa - Unfractionated heparin, LMW heparin and fondaparinux all inactivate factor Xa - LMH has limited inhibition of thrombin - Unfractionated heparin inhibits thrombin - Fonaparinux seems to have purely anti factor Xa activity • Metabolized in liver, excreted via kidney: Renal function does not effect unfractionated, but does effect LMW clearance by 10-40% & required dose reduction if CC <30mL/min • Unfractionated: o IV onset is instantaneous; Sub Q peak at 2-4 hrs w/ individual variation; T ½ is 45 min-1 hr; bioavailability also varies significantly - eg. Some proteins that competitively bind to receptor (AT etc) are acute phase reactants and are increased in the acutely ill patient = fewer sites for heparin to bind. o Benefits: • Rapid onset & Clearance • Monitoring via aPTT • Little/no renal metabolism • Reverses quickly with Protamine sulfate • IV or Sub Q o Limitations • Narrow therapeutic window • Highly variable dose response relationship • No oral • Complications eg. HIT, skin,osteoporosis if long term use • Little/no inactivation of thrombin if bound to fibrin, or factor Xa if bound to platelet = possible thrombus extension during heparin therapy • LMW: o SubQ peak is 3-5 hrs and after IV - 2 hrs; T1/2 is 2 hrs, steady state levels take 2-4 days. o Benefits: • Greater bioavailability • Outpatient treatment • Longer duration of effect - decreased dosing • Tighter relationship between dose & anticoagulant response - less titration of dose • Less risk of HIT and osteoporosis o Check platelets in first 10-14 days o Limitations • slight delay in onset • Longer duration of action • Less easily reversed with protamine sulfate • Prolonged T ½ in renal failure

FXaI: Apixaban (Eliquis)

• T1/2 = 5 to 9 hrs • Indication: o Prevention and treatment of VTE o Stroke prevention in pt w/ A Fib • Do not use in pregnancy or patients with prosthetic heart valves • Dosing o Fixed dose without monitoring • VTE prophylaxis w/ SX: 2.5mg po qd for 35 days (hip replacement) or 12 days (knee replacement) • Tx and 2ndary prevention of VTE: 10mg bid for 7 days then 5mg bid. If beyond 6 months reduce to 2.5mg bid • Stroke prevention w/A Fib: 5mg bid; or 2.5 mg bid if >80 y/o, weight <60Kg, serum creatinine > 1.5mg/dL • Least dependence on renal clearance of the factor Xa inhibitors • Not recommended if CC <15mL/min • Dose reduce if with drugs that both inhibit CYP-3A4 and P- glycoprotein (eg, ketoconazole) • Labs prior to use: platelet count, PT, aPTT, serum creatinine, liver function tests • Black Box Warning with neuraxial anesthesia

FXaI: Rivaroxaban (Xarelto)

• T1/2 = 7 to 17 hrs • Indication: o Prevention and treatment of VTE o Stroke prevention in pt w/ A Fib • Do not use in pregnancy • Dosing o Fixed dose without monitoring o 15 and 20 mg tablets, with food • VTE prophylaxis w/ SX: 10mg po qd for 35 days (hip replacement) or 12 days (knee replacement) • Tx and 2ndary prevention of VTE: 15mg bid for 21 days then 20mg qd • Stroke prevention w/A Fib: 20mg daily with evening meal or if CC < 50mL/min reduce to 15mg daily with evening meal • Not recommended if CC <30mL/min • Don't use if CC <15mL/min or significant hepatic impairment • Interacts with drugs that both inhibit CYP-3A4 and P-glycoprotein (eg, ketoconazole) • Labs prior to use: platelet count, PT, aPTT, serum creatinine, liver function tests • Black Box Warning with neuraxial anesthesia

Presentation • Joe is a 57 y/o male with a history of stage 3‐4 CKD and HTN who presents for a follow‐up visit • For the past few days he reports reports having nausea and vomiting • He estimates his urine output for the past day has been around 500ml • Joe is on the following medications: - Lisinopril 10mg daily - Low dose aspi ir n d il a y - Multivitamin daily Physical Examination • T‐ 97.8, P‐ 94 (supine), R‐16, BP‐ 104/78 (supine) • Cardiac: S1S2, RRR, no M/R/G • Lungs: CTA • ABD: Soft, nontender, nondistended with hyperactive bowel sounds • Extremities: no edema Question 1 • What else do you want to know about this patient? • How about orthostatic orthostatic vital signs? • How about a urinalysis? • What lab work might you want to order?• How about orthostatic vital signs? • How about a urinalysis? • What lab work might you want to order? Here is your data..... • BP standing is 100/62, P‐ 102 • Urinalysis: Specific gravity 1.016, no protein, no bl d oo , occasi l ona h li ya ne casts • Renal panel reveals serum creatinine 5.2 (up from 2.8 baseline)

• What is the most likely cause of this patient's acute kidney injury? • A. acute tub l u ar necrosis • B. prerenal azotemia • C. renal vein thrombosis • D. acute interstitial nephritis Rationale • Prerenal azotemia is the most likely culprit in this patient. Patients with chronic kidney disease are most susceptible to decreased perfusion pressure in dehydration. Postural hypotension occ rs u only in abo t u 50% of patients patients. N&V, relatively low BP, no edema and no specific urinalysis findings are consistent with prerenal azotemia. • The relatively normal UA helps exclude the other diagnoses.

Iron Deficiency Anemia

■ Average diet: 5-15 mg elemental iron, 10% absorbed (0.5-1.5 mg) ■ Most common physiologic cause: Menstruation - Avg menstrual flow 50 ml but can vary by 5X. ■ For men and postmenopausal women a good indicator of malignancy ■ Most common pathophysiologic cause: GI bleed - Bleeding ulcer, diverticular disease, hemorrhoids, Inflammatory Bowel Disease (1/3 of patients) ■ Others - Lead poisoning - Intravascular hemolysis (prosthetic heart valve) - GI: surgeries, malabsorption - Pregnancy Signs and Symptoms ■ Vary from none in mild anemia to severe with Hgb <7 ■ Mild (Hgb 10-12) : likely no symptoms ■ Moderate (Hgb 7-11): Palpitations, dyspnea, exercise intolerance, angular stomatitis, glossitis, pallor, Koilonychias ■ Severe (Hbg < 7): postural hypotension, dizziness, weak, gastritis, paresthesias, lethargy Diagnosing: CBC ■ Low MCV ■ Low MCH ■ High RDW (>15) ■ Low reticulocyte count (although can be increased in chronic GI bleed) Iron Studies ■ Serum Ferritin ■ Transferrin ■ Transferrin Saturation ■ Serum Iron ■ Total Iron Binding Capacity ■ *One way to 'tease out' if this is IDA...... - Trial of iron supplementation Once IDA is suspected/confirmed get FOBT 10ml blood loss/day to get a positive reading Development of the anemia ■ Occurs in stages ■ Mild may see normal MCV but low Ferritin ■ While RBC formation continues in presence of low iron supply the iron stores are depleted ■ Serum iron falls, Transferrin increases, Transferrin saturation decreases, TIBC increases ■ MCV begins to fall....microcytic cells, ■ MCH falls....hypochromic cells ■ As anemia worsens: anisocytosis, poikilocytosis Treatment of IDA ■ Find The Cause.....the anemia is the response to another pathology ■ Oral iron - Ferrous sulfate 300mg (60mg elemental iron) tid - Ferrous gluconate 320 mg (36mg elemental iron) tid - Best absorbed in acidic environment ■ Nausea, constipation are common SE and reasons for non-compliance ■ Goal: - Reticulocytosis within days - Increased Hgb by 1-2 g/dl every 2 weeks, serial CBC's - Restoration of iron stores in 3-4 months ■ Post treatment Ferritin is good indicator of treatment success ■ Parenteral Iron - Preparations: ■ Iron sucrose (Venofer) - Less allergic reaction - Effective for pregnant/postpartum IDA ■ Iron Dextran (INFed, DexFerrum) - Can be contraindicated in acute renal failure - Higher molecular weight, released more slowly - Can supply entire iron need in one dose (200-500mg) - Requires a small test dose d/t anaphylaxis risk - SE: myalgia, arthralgia, N/V, fever. Hypotension ■ Erythropoetin: (CA, AIDS, IBD, ESRD) - Very expensive

Microcytic Anemias

■ Iron deficiency anemia ■ Anemia of Chronic disease ■ Thalassemias