Heme/Immuno
Which disorder occurs in which which the immune system mistakenly attacks normal proteins in the blood cause blood clots to form within the arteries, veins, and organs.
Antiphospholipid syndrome
Budd-Chiari syndrome
Budd-Chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow (may be from thrombus or not) Triad of abdominal pain, ascites, & hepatosplenomegaly
Polycythemia vera- clinical presentation , labs, dx
Expanded blood volume & ↑ blood viscosity: •HA, dizziness, tinnitus, blurred vision, fatigue *Aquagenic pruritis* (pruritis after warm bath/shower) *histamine release from excess basophils *Erythromelalgia* •burning pain in hands/feet w/ erythema, pallor, or cyanosis Thrombosis (e.g., CVA, MI, DVT, PE, superficial) •Budd-Chiari syndrome (triad of abdominal pain, ascites, & hepatosplenomegaly) Hemorrhage (e.g., epistaxis d/t mucosal engorgement & platelet dysfunction) LABS: ↑ WBC >10,500/μL,↑ platelets >450,000/μL, ↑ LDH, ↑ B12, ↑ uric acid Diagnosis: Increased RBC volume (>hematocrit and hemoglobin) Bone marrow biopsy
Hemolytic Uremic Syndrome (HUS) clinical presentation, tx
PATHO: exotoxins (shiga-like & shiga toxins) damages vascular endothelium, activating platelets -> microthrombosis of small vessels -> consumptive thrombocytopenia & hemolytic anemia •predominantly seen in *children w/ diarrhea prodrome*: Enterohem. E coli O157:H7 (80%), Shigella, Salmonella TRIAD: "RAT" •renal failure/uremia (predominant symptom) •anemia: microangiopathic hemolytic anemia *jaundice •thrombocytopenia: bruising, purpura, bleeding Thrombocytopenia Hemolytic anemia: •peripheral smear: ↑ reticulocytes, schistocytes (bite or fragmented cells) •LFTs: ↑ indirect bilirubin, ↓ haptoglobin ↑ BUN/creatinine Tx: observation in most children (usually self-limited) - plasmapheresis - +/- FFP if severe **NO ABX - may worsen the disease**
Pernicious anemia
Its an autoimmune disorder and is a common cause of vitamin B12 deficiency. Gastric parietal cells produce intrinsic factor, which is necessary for 99% of the absorption of vitamin B12. In pernicious anemia, autoantibodies destroy the gastric parietal cells or neutralize intrinsic factor, preventing vitamin B12 from being absorbed by terminal ileum. Pernicious anemia is diagnosed by laboratory testing. Complete blood count (CBC) typically shows a macrocytic, normochromic anemia Pernicious anemia may be treated with high doses of oral or sublingual vitamin B12 (1,000-2,000 mcg daily) after an initial parenteral loading dose
Treatment for polycythemia vera if history of thrombosis
Low-risk (≤60yo, ⊖hx of thrombosis): •phlebotomy to maintain Hct <45% •ASA 81mg •NO iron supplementation *encourage low-iron diet High-risk (>60yo, ⊕hx of thrombosis): •phlebotomy to maintain Hct <45% •ASA 81mg •cytoreductive therapy w/ Hydroxyurea
A 35-year-old woman presents to the emergency department with slurred speech and right facial drooping. She had a similar episode a few months ago and did not experience any residual effects. She also has a history of deep vein thrombosis in the left leg and a second-trimester spontaneous abortion. She has no history of hypertension or diabetes. Vital signs demonstrate a BP of 148/88 mm Hg, HR of 104 bpm, RR of 15/min, SpO2 of 98%, and T of 99.0°F. Physical examination reveals impaired facial muscle strength on the right, decreased right upper extremity strength, and hyperreflexia of the right upper and lower extremity. An ECG reveals sinus tachycardia. Which of the following should be included in the evaluation to determine the cause of this condition? one marrow biopsy BD-dimer CHemoglobin electrophoresis DLupus anticoagulant EOsmotic fragility testing
Lulus anticoagulant Antiphospholipid syndrome is an acquired autoimmune disorder that causes a hypercoagulable state. Individuals with this disorder are known to have recurrent venous or arterial thrombosis at an early age,
Factor V Leiden
MC inherited cause of hypercoagulability (thrombophilia) PATHO: mutated factor V is resistant to breakdown by activated protein C (V doesnt listen to C anymore!), leading to increased hypercoagulability Clinical manifestations: Venous thromboembolism (DVT, PE) Unexplained late pregnancy loss(es) Dx •activated protein C resistance assay (+) à confirm w/ DNA testing •DNA testing: mutation analysis Tx indefinite anticoagulation
CLL
MC leukemia in adults lymphocytosis smudge cells
G6PD Deficiency is what type(s) of disorder
Normocytic, hemolytic anemia
Thrombotic Thrombocytopenic Purpura (TTP)- patho, risk
PATHO: auto-ab vs. ADAMTS13 (vWF-cleaving protease) unusual large vWF multimers -> micro thrombosis of small vessels ->thrombocytopenia (consumptive) & hemolytic anemia Incidence: •young adults 20-50yrs •MC women
A 65-year-old man with hepatocellular carcinoma presents to the emergency department with acyanotic skin. He does not use tobacco. Physical examination reveals acrocyanosis but is otherwise normal. Laboratory studies show a white blood cell count of 7,500 cells/mm3, hematocrit 56%, hemoglobin 17.5%, and platelet count 250,000/microL. Serum erythropoietin is found to be elevated. JAK2 mutation test is negative. Which of the following is the most likely diagnosis? Essential thrombocytosis BPolycythemia vera CSecondary polycythemia DSpurious polycythemia
Secondary Secondary polycythemia refers to an increase in red blood mass due to elevated serum erythropoietin caused by a physiologic response to tissue hypoxia (most common cause) or by a tumor
B12 vs Folate deficiency
Serum methylmalonic acid is elevated in vitamin B12 deficiency and normal in folate deficiency. Homocysteine levels are elevated in both vitamin B12 deficiency and folate deficiency
HUS triad
TRIAD: "RAT" •renal failure/uremia (predominant symptom) •anemia: microangiopathic hemolytic anemia *jaundice •thrombocytopenia: bruising, purpura, bleeding
A 25-year-old man presents to the emergency department with recurrent epistaxis, gum bleeding, and easy bruising. Physical examination is normal. Laboratory studies reveal normal platelet, normal prothrombin, abnormal activated partial prothrombin time, and prolonged bleeding time. =
Von Willebrand disease tx: desmopressin
Hemophilia A - what, s/s, dx, tx
X linked - often in males Deficiency in factor 8 hemophilia AAA-888 S/s Hemarthrosis: delayed bleeding or swelling in weight- bearing joints (MC ankles) Excessive hemorrhage due to trauma & surgery or incisional bleeding Dx: PT normal PTT prolonged factor 8 assay: decreased or absent Tx Desmopressin aka DDAVP (helps with vMF which helps with factor 8) Factor 8
Hemophilia B what, s/s, dx, tx
factor 9 deficiency "Benign, B9* Hemarthrosis: delayed bleeding or swelling in weight- bearing joints (MC ankles) Excessive hemorrhage due to trauma & surgery or incisional bleeding Dx: PT normal PTT prolonged Tx factor IX infusion no desmopression -only helps factor 8
If macrocytic anemia is found and the mean corpuscular volume is > 115 fL what should be suspected
folate deficiency or B12 deficiency If both vitamin B12 and folate are borderline, methylmalonic acid and homocysteine levels can be obtained to distinguish between them.
Alpha Thalassemia is what type of disorder
microcytic anemia MC in SE Asians
Ristocetin added to Von Willebrand diseased blood will result in
no aggregation of platelets
CML
philedelphia chromosome leukocytosis - increase in leukocytes (~100,000 uL) thrombocytosis
G6PD Deficiency treatment
Usually self-limited; avoid offending foods & drugs •Hgb returns to normal within 3-6wks Hgb >7mg/dL + clinically stable + no hemoglobinuria: observe for 24-48h Hgb <7mg/dL or Hgb 7-9mg/dL w/ continued brisk hemolysis (persistent hemoglobinuria): consider PRBC transfusion neonatal jaundice: phototherapy
Macrocytic anemia = mean corpuscular volume would be?)
> 100 fL
ALL
>20% lymphoblasts MC children Bone pain painless LAD
AML
>20% myeloblasts Auer rods older people anemia thrombocytopenia
Von Willebrand Disease -
Decrease in the quality or quantity of vWF (in turn leading to degradation of factor 8) Clinical manifestations: Mucocutaneous bleeding: epistaxis, bleeding gums, petechiae bruising prolongedbleeding time after minor cuts Dx -prolonged PTT & bleeding time (worse w/ aspirin) -Ristocetin-induced platelet aggregation (gold standard) Tx - DDVAP - factor VIII concentrates - VWF-containing products
A 26-year-old previously healthy woman presents to the emergency department with dyspnea, fatigue, and dark urine which began after gardening on a very warm day. Physical exam reveals jaundice and tachycardia, but vital signs are otherwise normal. Skin turgor and abdominal exam are within normal limits. Laboratory analysis reveals a hemoglobin of 7 g/dL, reticulocyte count of 10%, and lactate dehydrogenase level of 600 U/L. Which of the following additional tests is the best choice to aid in diagnosis of this patient's condition? Direct antiglobulin test Hemoglobin electrophoresis Rapid diagnostic test for malaria Sedimentation rate
Direct antiglobin test Hemolytic anemia refers to a low red blood cell count due to increased destruction of red blood cells Complete blood count with peripheral smear will reveal low red blood cells, hemoglobin, and hematocrit. A reticulocyte count is essential to obtain and will be elevated in hemolytic anemia. Lactate dehydrogenase will be elevated. If these tests are consistent with hemolysis and no obvious etiology is apparent, the next test to obtain is a direct antiglobulin test. This test will be positive in autoimmune hemolytic anemia
MC inherited cause of hypercoagulability (thrombophilia)
Factor V Leiden Mutation
Antiphospholipid Syndrome -hallmark / clinical manifestations, diagnostics and treatment
HALLMARK: thrombotic events (venous > arterial) - MC venous site: lower extremity DVT •superficial vein thrombosis, PE - MC arterial site: cerebral (i.e., stroke or TIA) HALLMARK: pregnancy complications - 1+ fetal death >10wks gestation - premature birth d/t preeclampsia/placental insufficiency - 3+ unexplained embryonic losses (<10wks gestation) •thrombocytopenia, livedo reticularis LABS: CBC, CMP, UA Antiphospholipid Antibody Testing: •&anticardiolipin antibodies (aCL)*, IgG/IgM (ELISA) *false⊕ RPR •*anti-β2 glycoprotein I (aβ2GPI) antibodies*, IgG/IgM (ELISA) •*lupus anticoagulant (LA) functional coagulation assay* Acute thrombosis: •anticoagulate w/ Warfarin (INR 2-3) *preferred vs DOACs Secondary thrombosis prevention: •VTE: Warfarin *lifelong •Arterial: Warfarin + ASA *lifelong Pregnancy: LMWH *NO WARFARIN
Which of the following leads to hemolytic anemia? Immune Thrombocytopenic Purpura (ITP) Hemolytic Uremic Syndrome (HUS) Thrombotic Thrombocytopenic Purpura (TTP) Heparin Induced Thrombocytopenia (HIT) Disseminated Intravascular Coagulation (DIC)
Hemolytic Uremic Syndrome (HUS) Thrombotic Thrombocytopenic Purpura (TTP) Disseminated Intravascular Coagulation (DIC)
DIC -what will be seen in labs
Hemolytic anemia: •peripheral smear: ↑ reticulocytes, schistocytes (bite or fragmented cells) •LFTs: ↑ indirect bilirubin, ↓ haptoglobin *abnormal coagulation tests ↓ fibrinogen (all used up!) ↑ D-dimer, PT, & PTT Severe thrombocytopenia
Treatment for HIT
Immediate D/C of all heparin + initiation of non-heparin anticoagulants (because we still need the anticoag) •direct thrombin inhibitors (argatroban)
Hereditary Spherocytosis
PATHOPHYSIOLOGY • Deficiency in RBC membran e & cytoskeleton (spectrin), leading to increased RBC fragility & sphere-shape d RBCs. These abnormal RBCs are detected & destroyed by the spleen (hemolysis). CLINICAL MANIFESTATIONS • Broad spectrum of clinical presentations. Severe cases may present in infancy (eg, neonatal jaundice). Mild cases may present in adulthood. • Recurren t episode s of hemolysis (anemia , jaundice, & splenomegaly) hallmark; pigmented gallstones (calcium bilirubinate). DIAGNOSIS • Periphera l smear: - hvpERchromic microcytosis. 80% spherocyte s (round RBCs that lack central pallor). - May have a hemolytic smear (schistocytes, increased reticulocytes). - 'Increased MCHC most reliabl e (mean corpuscular hemoglobin concentration). EMA binding: preferred test (most accurate). Negative Coombs testing: Coombs negativity distinguishes Hereditary spherocytosis from Autoimmune hemolytic anemia MANAGEMENT • Folic acid not curative but helpful to sustain RBC production & DNA synthesis. • Splenectomy curative in sever e o r refractory diseas e (stops
Thrombotic Thrombocytopenic Purpura (TTP)- clinical presentation, dx, tx
PENTAD: "FAT RN" •fever •anemia: microangiopathic hemolytic anemia ->*jaundice •thrombocytopenia: bruising, purpura, bleeding •renal failure/uremia •neuro sxs: HA, CVA, AMS Dx: Thrombocytopenia Hemolytic anemia: •peripheral smear: ↑ reticulocytes, schistocytes (bite or fragmented cells) •LFTs: ↑ indirect bilirubin, ↓ haptoglobin Normal coagulation tests Tx - plasmapheresis: removes Ab & adds ADAMTS13 - immunosuppression: steroids, cyclophosphamides
Thrombosis prevention for pregnant patient
Pregnancy: LMWH *NO WARFARIN
G6PD Deficiency-presentation, dx
Presentation Most patients are asymptomatic until times of oxidative stress. • Episodic hemolytic anemia: symptoms begin 2-4 days after exposure. Back or abdominal pain, symptoms of anemia, jaundice (indirect bilirubin, dark urine), •neonatal jaundice Dx: Peripheral smear: *normocytic hemolytic anemia only during crises - schistocytes ("bite" or fragmented cells). +Heinz bodies hallmark. Smear is usually normal when not in acute stage. • Hemolytic anemia: increased reticulocytes, increased indirect bilirubin, decreased haptoglobin.* • Enzyme assay for G6PD: eg, Fluorescent spot test. DNA testing. Usually performed after episodes. MANAGEMENT • Usually self-limited - avoid offending food & drugs, treat underlying infection etc. • Severe anemia: iron and folic acid supplementation. Blood transfusions if severe. • Neonatal jaundice: phototherapy first-line. Exchange transfusion if refractory.
A male infant is born by vaginal delivery and has a subgaleal hematoma. The mother is a known carrier of hemophilia A. Which of the following diagnostic findings in the infant supports a diagnosis of hemophilia A? Prolonged partial thromboplastin time Prolonged prothrombin time Reduction in factor IX activity Reduction in von Willebrand factor
Prolonged partial thromboplastin time
Warfarin induced skin necrosis is seen in which disorder
Protein C or S Deficiency
Protein C or S Deficiency- define what these proteins do, etiology of disease, dx ,tx
Proteins C & S are vitamin K-dependent anticoagulant proteins produced by the liver that stimulate fibrinolysis & inactivate factors V & VIII (protein S and C =Stop Clots) •decreased protein C or S leads to *hypercoagulability* Etiologies: •inherited: autosomal dominant (C MC) •acquired: ESLD, severe liver disease S/S Increased incidence of DVT/PE Warfarin-induced skin necrosis Newborns: purpura fulminans: red purpuric lesions at pressure points, Dx •protein C & S functional assay, plasma protein C & S antigen levels Tx Thrombosis: - *protein C concentrate* - *indefinite anticoagulation* Warfarin-induced necrosis: - immediately discontinue warfarin - admin. IV vitamin K, heparin, protein C concentrate, or FFP
A 5-year-old girl is brought to the clinic for evaluation of petechiae. The parents report she has had no fever, decreased appetite, bone or joint pain, or weight loss. She had a cold and runny nose about a month ago. On physical exam, the girl appears well and has vital signs within normal limits, as well as petechiae and purpura on the upper and lower extremities. There are no signs of mucosal bleeding, and the lymph nodes, liver, and spleen are unremarkable. Laboratory studies reveal a platelet count of 40,000/µL and a complete blood count otherwise within the reference range, with a prothrombin time of 11 seconds and an activated partial thromboplastin time of 31 seconds. Which of the following is the most likely diagnosis? Factor VIII deficiency Hemolytic uremic sydrome Immune thrombocytopenia Leukemia Thrombotic thrombocytopenic purpura
The girl has symptoms and laboratory findings consistent with immune thrombocytopenia (ITP), which was previously referred to as idiopathic or immune thrombocytopenic purpura. ITP is one of the most common causes of symptomatic thrombocytopenia in children. no systemic symptoms or prior history of bleeding or significant disease. Almost all patients diagnosed with ITP have signs of cutaneous bleeding that include petechiae, purpura, and ecchymoses. Laboratory findings reveal thrombocytopenia, which is usually the only abnormality detected.
How to diagnose Heparin Induced Thrombocytopenia (HIT) /gold standard
The patient will experience acquired thrombocytopenia esp. within the first 5-10d of the initiation of heparin Thrombocytopenia - bleeding Thrombosis - venous thrombosis, gangrene, organ infarction, skin necrosis Labs •thrombocytopenia •timing of platelet drop (>50%) •thrombosis Gold standard: 14-C-serotonin release assay
Question: What is a possible finding in the oral cavity in patients with folate deficiency?
aphthous ulcers
MC hereditary bleeding disorder
von Willebrand disease
G6PD Deficiency -etiology, patho, risk factors, exacerbating factors
x-linked recessive enzymatic disorder of RBCs that may cause episodic hemolytic anemia Risk Factors: males, AA males PATHO: decreased G6PD activity during oxidative stress results in an oxidative form of Hb (methemoglobin); the *denatured hemoglobin precipitates as Heinz bodies* Exacerbating factors: •infection MC cause, fava beans •dapsone, methylene blue, primaquine, nitrofurantoin, phenazopyridine
Immune Thrombocytopenic Purpura (ITP)
· Acquired disorder in which there is immune-mediated destruction of platelets · In children, it is usually an acute disease, most commonly following an infection, and with a self-limited course S/S · thrombocytopenia incidentally found on a routine CBC · ecchymoses and petechiae Labs/Work up Complete blood count (CBC) with platelets and peripheral blood smear · Low (often very low) platelet count (thrombocytopenia) Tx Patients without significant bleeding symptoms, without severe thrombocytopenia or without signs of impending bleeding can be treated as outpatient: · prednisone at 1 mg/kg or a 4-day course of dexamethasone, 40 mg/d
Polycythemia vera - etiology, patho, risk factors
•acquired clonal myeloproliferative disorder •overproduction of all 3 hematopoietic cell lines *most prominently RBCs •MCC of primary erythrocytosis PATHO: JAK2 mutation •erythroid production independent of EPO RF: 60yo is median age at diagnosis, men
Antiphospholipid Syndrome -etiology and patho
•autoimmune disorder •arterial/venous thromboembolic events •recurrent pregnancy loss •persistent antiphospholipid antibodies PATHO: antiphospholipid antibodies induce cellular activation resulting in multiple procoagulant/inflammatory effects & activation of complement = thrombosis
