Apex Fluids & Blood

Name 2 antifibrinolytics and 4 fibrinolytics

-Antifibrinolytics stop the conversion of plasminogen to plasmin, they promote clot formation → Tranexamic acid, aminocaproic acid -Fibrinolytics facilitate the conversion of plasminogen to plasmin. They break down clots → tPA, urokinase, reteplase, alteplase

What is the treatment for hemophilia A?

-Factor VIII concentrate prior to surgery -FFP and cryoprecipitate can also be used to replace factor VIII, however their use increases the risk of transfusion related disease -Antifibrinolytics (tranexamic acid or aminocaproic acid) can be used to minimize bleeding during dental procedures -A type and crossmatch is required for any surgical procedure

Why do neonates receive vitamin K after birth?

-Healthy intestinal flora is required for the gut to synthesize vitamin K -Neonates don't have the intestinal flora that synthesizes vitamin K, so 0.5-1 mg IM after delivery is common

How is hemophilia B different from hemophilia A?

-Hemophilia B is a factor 9 deficiency. -Labs and anesthetic management are similar to hemophilia A with 1 exception → Factor IX concentrate is used instead of factor VIII

How does protamine reverse heparin?

-Heparin is a large negatively charged particle -Protamine is a highly alkaline compound with a strong positive charge -The positive charge of protamine and the negative charge of heparin neutralize each other and stop heparin's anticoagulant activity

What is the risk associated with IV phytonadione?

-Life-threatening anaphylaxis, IV administration is best avoided. However, if given by this route, the rate should not exceed 1 mg/min

Describe the process of fibrinolysis

-Plasminogen is a proenzyme that is synthesized in the liver. It is incorporated into the clot as it's being formed, but it lays dormant until it is activated -Plasmin is a proteolytic enzyme that degrades fibrin into fibrin degradation products

What is the treatment of vaso-occlusive crisis?

-Sickled cells → impaired tissue perfusion → ischemic injury -Most common manifestation of sickle cell disease -Treatment → analgesics and hydration -Hydroxyurea reduces the incidence and severity of vaso-occlusive crisis

What are the 3 types of Von Willebrand disease?

-Von Willebrand disease is the most common inherited disorder of platelet function, the platelet count is normal, but the platelets do not function properly. -Type I: Mild-moderate reduction in the amount of vWF produced -Type II: The vWF that is produced doesn't work well -Type III: Severe reduction in the amount of vWF produced

Describe the pathophysiology of hemophilia A

-X-linked chromosomal disorder (more common in males) that causes factor VIII deficiency -Severe disease (Factor VIII activity < 1%) is associated with spontaneous bleeding into the joints, muscles, and vital organs

Treatment for hypercalcemia

0.9% NaCl Loop diuretic - furosemide

What factors are part of the final common pathway?

1, 2, 5, 10, 13 The final common pathway can be purchased at the five and dime for 1 or 2 dollars on the 13th of the month

What are the 3 steps of platelet plug formation? (Primary hemostasis?)

1. Adhesion 2. Activation 3. Aggregation PLT plug is formed in ~5 minutes

Describe the Starling forces in

1. Hydrostatic Pressure: pressure exerted by fluid Pc = capillary hydrostatic pressure - pushes fluid out of capillary Pie if- Interstitial oncotic pressure (pulls fluid out of the capillary) 2. Osmotic Pressure: pressure exerted by movement of fluid in response to solute concentration Pif = interstitial hydrostatic pressure (pushes fluid into capillary) pie-C = capillary oncotic pressure (pulls fluid into capillary)

What are the 4 steps of hemostasis?

1. Vascular spasm 2. Formation of the platelet plug (primary hemostasis) 3. Coagulation and the formation of fibrin (secondary hemostasis) 4. Fibrinolysis when the clot is no longer needed

What is the reference value for plasma osmolarity, and what are the 3 most important contributors?

280-290 mOsm/L 3 most important determinants sodium, glucose and BUN

What are examples of hypertonic solutions- both crystalloids and colloids

3% NS D5NS D51/2 NS D5LR 10% dextran

How long before surgery should you discontinue heparin?

6 hours

What is the concern about an Rh-negative mother and pregnancy?

A person who is Rh- can be sensitized by exposure to Rh+ blood during transfusion or pregnancy. An Rh- mother can be sensitized by an Rh+ fetus. Transfer occurs across the placenta. The mother receives Rhogam to prevent sensitization If the mother becomes sensitized and develops antibodies, a subsequent pregnancy with an Rh+ fetus may result in erythroblastosis fetalis

How do you treat a patient with ATIII deficiency?

AT III concentrate or FFP Common cause for failure to achieve anticoagulation despite adequate heparin dosing prior to CPB

List 3 examples of GIIb/IIIa receptor antagonists, and state how long each must be discontinued prior to surgery

Abciximab - 3 days Eptifibatide - 1 day Tirofiban - 1 day

Etiologies of metabolic alkalosis

Addition of HCO3- D/t HCO3 administration, or massive transfusion (liver converts preservatives to HCO3) Loss of Nonvolatile acid- Loss of gastric fluid, vomiting, NG suction, loss of acid inurine, diuretics, ECF depletion Increased mineralocorticoid activity- Cushing's syndrome, hyperaldosteronism

Disadvantages of Colloids

Albumin- binds Ca = hypocalcemia FDA black box warning on synthetic colloids d/t risk of renal injury Coagulopathy Dextran > hetastarch > hextend Don't exceed 20ml/kg Anaphylactic potential Highest risk = dextran

Discuss the relationship between blood type, erythrocyte antigens, and plasma antibodies

Blood type is determined by specific glycoproteins present on the RBC cell membrane. These glycoproteins have an antigenic potential, so administering blood of the wrong type has catastrophic consequences. The most clinically important antigens are the ABO and Rh systems. If the antigen is expressed on the erythrocyte, then there will NOT be an antibody against that specific antigen in the plasma. If an antigen is NOT expressed on the RBC, then there WILL be an antibody against that specific antigen in the plasma.

What is the difference between osmolarity and osmolality?

Both are measures of concentration- the amount of solvent within a defined space Osmolarity- measures the number of osmoles per liter of solvent Osmolality- number of osmoles per kg of solvent

What is the MOA for COX inhibitors? Which agents provide irreversible COX inhibition?

COX inhibitors prevent PLT aggregation by blocking cyclooxygenase 1 (COX-1). This stops the conversion of arachidonic acid to prostaglandins, and ultimately thromboxane A2 ASA is irreversible- lasts the life of the PLT NSAIDs are reversible- duration is shorter than life of the PLT

Treatment for hypermagnesemia

Calcium chloride

List the treatment options for hyperkalemia

Calcium- stabilizes cardiac membrane Insulin + D50 Hyperventilation HCO3 Albuterol Potassium wasting diuretics Dialysis

Type 1 and type 2 heparin induced thrombocytopenia

Causes clot formation throughout the body HIT occurs when the body mounts an immune response against heparin after it binds to PLT factor 4. IgG antibodies activate PLTs, which ultimately results in uncontrolled clot formation. The PLT count falls because PLT are consumed faster than they are produced.

What complication can result when hypertonic saline is administered too quickly?

Central pontine myelinolysis

Describe the pathophysiology of DIC

Characterized by disorganized clotting and fibrinolysis that lead to the simultaneous occurence of hemorrhage and systemic thrombosis Generalized thrombin formation creates microvascular clots that impair tissue perfusion, resulting in tissue hypoxia and acidosis. The body attempts to break down these clots by activating its anticoagulant system, however this leads to widespread consumption of clotting factors, fibrinogen, and PLT.

List 4 examples of ADP receptor inhibitors, and how long each must be discontinued prior to surgery

Clopidogrel - 7 days Ticlopidine - 14 days Prasugrel 2-3 days Ticagrelor 1-2 days

Under normal conditions, why does blood remain a liquid?

Coagulation proteins circulate in the inactive form Endothelium is smooth, glycocalyx repels clotting factors Undamaged endothelium does not express tissue factor or collagen. This prevents activation of PLT and the coagulation cascade. Activated factors are removed by brisk blood flow through the vessels as well as anticoagulants in circulation.

Aside from desmopressin, list 3 other treatments that can improve the coagulopathy of Von Willebrand disease?

Cryoprecipitate contains factors 8, 13, fibrinogen and vWF. Can be used for type 1, 2, or 3 disease FFP contains all the clotting factors- can be used for all types of vWD Purified VIII-vWF concentrate reduces the risk of transfusion related infection. It is the first line agent for patients with type 3 disease

What are examples of hypotonic solutions?

D5W NaCl 0.45%

What is the MOA for desmopressin? What is the dose?

DDAVP is a synthetic analog of ADH. It stimulates the release of endogenous vWF and increases factor 8 activity. Patients with type 1 disease respond best to desmopressin. Patients with type 3 disease do not respond to desmopressin because they don't produce vWF. Dose is 0.3-0.5 mcg/kg IV SE- hypotension with rapid administration

CNS effects of alkalosis

Decreased CBF Decreased ICP

Cardiac effects of alkalosis

Decreased P50 Decreased coronary blood flow Increased risk of dysrhythmias

Management of the patient with DIC

Definitive = treat underlying cause. Otherwise supportive Hypovolemia- IVF Coagulopathy- replace consumed blood components with FFP, PLT, and cryo Severe microvascular thrombosis-IV heparin or LMWH

What blood type is the universal donor for FFP? What about universal acceptor?

Donor = AB+ Acceptor = O-

What blood type is the universal donor for RBC? What is the universal acceptor?

Donor = O- Acceptor = AB+

How does hyperkalemia affect the EKG?

Early = long PR, peaked T wave, short QT Middle- flat P, wide QRS Late- QRS progresses to sine wave then to VF

Describe the pathophysiology and treatment of factor V Leiden mutation

Factor V Leiden causes a resistance to the anticoagulant effect of protein C Treatment- only patients with thromboembolism require anticoagulation. Lifelong anticoagulation is unwarranted unless the patient experiences recurrent thrombotic events.

What is lymph and how does the lymphatic system work?

Fluid scavenger- removes fluid, protein, bacteria, and debris that has entered the interstitium. It accomplishes this goal with a pumping mechanism that propels lymph through a vessel network lined with one-way valves. This creates a net-negative pressure in the interstitial space. Edema occurs when the lymphatic system is unable to do its job.

Where are PLT formed? Where are they metabolized?

Formed by megakaryocytes in the bone marrow Cleared by macrophages in the reticuloendothelial system and the spleen

How does dextrose affect the tonicity of IVF?

Glucose is metabolized to carbon dioxide and water = Water is hypotonic

Possible causes of non-gap acidosis

HARDUP hypoaldosteronism acetazolamide Renal tubular acidosis diarrhea ureterosigmoid fistula pancreatic fistula Large volume resuscitation with NaCL= non gap metabolic acidosis with hyperchloremia

What are the doses of heparin for CPB and protamine?

Heparin - 300-400 u/kg Protamine dose- 1mg for every 100U of heparin predicted to be in circulation

What is the MOA of heparin?

Heparin inhibits the intrinsic and final common pathways Antithrombin III is a naturally occuring anticoagulant that circulates in the plasma. Heparin binds to AT and greatly accelerates its anticoagulant activity. The heparin-AT complex neutralizes thrombin and activated factors X, XII, XI, and IX

Misc. effect of alkalosis

Hypokalemia Decreased ionized calcium

What are the SE of protamine?

Hypotension - d/t histamine release, give over 5 minutes Pulmonary HTN- TxA2 and serotonin release Allergic reaction- previous sensitization to NPH insulin Fish allergy

What is the relationship between the tonicity of IV solutions and increased ICP?

Hypotonic solutions have a lower osmolarity than the plasma. These fluids are the same as giving free water, and this free water distributes throughout all the body compartments. This is why hypotonic solutions are poor expanders of intravascular volume, and also why you should never give a hypotonic solution to a patient with an increased ICP. It will cause the cells to swell, increase their volume, and increase ICP. Hypertonic solutions are useful for treating cerebral edema (pulls water out of cells causing them to shrink)

What factors are in the extrinsic pathway?

III, VII Extrinsic pathway can be purchased for 37 cents

CNS effects of acidosis

Increased CBF Increased ICP

Cardiac effects of acidosis

Increased P50 Decreased contractility Increased SNS tone Increased risk of dysrhythmias

What lab results are consistent with DIC?

Increased PT, PTT, and D-Dimer Decreased PLT and fibrinogen

What lab results are consistent with Von Willebrand disease?

Increased PTT Increased bleeding time

Pulmonary effects of acidosis

Increased pulmonary vascular resistance

MOA of warfarin

Inhibits the enzyme vitamin K epoxide reductase complex 1, which is responsible for converting inactive vitamin K to active vitamin K Indirectly blocks the manufacture of the vitamin K dependent factors- 2, 7, 9, 10 and protein C&S

What are the 3 phases of the contemporary cell-based coagulation cascade?

Initiation Amplification Propagation

What lab results are consistent with hemophilia A?

Intrinsic pathway = increased PTT

How do isotonic IVF distribute in the patient?

Isotonic solutions have an osmolarity that is very close to the plasma. These solutions expand the plasma volume and the ECV Crystalloids tend to remain in the intravascular space for ~ 30 minutes before moving to the ECF.

Disadvantages of crystalloids

Limited ability to expand plasma volume- increases volume for 20-30 minutes. Increases potential for peripheral edema. Large volume of NaCl = hyperchloremic metabolic acidosis. Increased chloride causes increased bicarb excretion by the kidney Dilutional effect on albumin- reduces capillary oncotic pressure Dilutional effect on coagulation factors

Presentation of hypermagnesemia

Loss of DTRs 4-6 mEq/L or 10-12 mg/dl Respiratory depression - 6.5-7.5 mEq/L or > 18mg/dl Cardiac arrest- >10 mEq/L or > 25mg/dl

How is lymph returned to the systemic circulation?

Lymph is returned to the venous circulation by way of the thoracic duct at the juncture of the internal jugular and subclavian vein. You can injury the thoracic duct during venous cannulation. Since the thoracic duct is larger on the left side, there is a greater risk of chylothorax (lymph in the chest) during left sided IJ insertion

Causes of anion gap acidosis

MUDPILES: Methanol Uremia Diabetic ketoacidosis Paraldehyde or Phenformin Iron tablets or Isoniazid Lactic acidosis, Ethylene glycol Salicylates

What are examples of isotonic solutions- both crystalloids and colloids

NaCl 0.9% LR Plasmalyte A 5% albumin 6% voluven 6% Hespan

What is the normal value for PLT? What are the critical values?

Normal 150,000-300,000 < 50,000 increases surgical bleeding risk < 20,000 increases spontaneous bleeding risk

What is the normal ACT? What value should be achieved prior to transitioning to CPB?

Normal is 90-120 Should be >400 prior to CPB ACT is measured before heparin administration, 3 minutes after it's given, and every 30 minutes after

What is the difference between osmosis and diffusion?

Osmosis- net movement of water across a semipermeable membrane, where the direction of water movement is driven by the difference in solute concentration on either side of the membrane (only the solvent moves) Diffusion is the net movement of molecules from a region of high concentration to a region of low concentration (solvent and solute move)

What is osmotic pressure, and what is its primary determinant?

Osmotic pressure is the pressure of a solution against a semipermeable membrane that prevents water from diffusing across that membrane. Osmotic pressure is a function of the number of osmotically active particles in solution. Not a function of molecular weights

Triggers that cause sickling of Hgb S

Pain Hypothermia Hypoxemia Acidosis Dehydration Anesthetic management focuses on avoiding these triggers

What is the role of recombinant factor 7 in the management of hemophilia A and B?

Patients with hemophilia A or B can develop inhibitors that prevent exogenous factor 8 or 9 from achieving a therapeutic goal. For a clot to form, the missing coagulation factor must be replaced or "bypassed". Recombinant factor 7 is a "bypass" agent because it skips over factor 8 or 9 in patients with inhibitors, allowing the patient to form clot. Dose is 90-120 mcg/kg Can also be used as "last-ditch" treatment for bleeding without identifiable cause. Dose is 20-40mcg/kg

Which populations tend to have a greater percentage of TBW % by weight? Which have less?

Populations with higher TBW - Neonates Populations with lower TBW - females, obese, elderly

How does hypermagnesemia affect neuromuscular blockade?

Potentiates NMB

Describe the pathophysiology and treatment of protein C and S deficiency

Protein C produces an anticoagulant effect by inhibiting factors Va and VIIIa. This creates a feedback mechanism that prevents unnecessary clot formation. Protein S is a co-factor of protein C. (Helps it do its job) Deficiency in C or S can produce hypercoagulable state = increased risk of thrombosis Treatment- a thromboembolism is treated with heparin and transitioned to warfain. Patient's may or may not require life-long anticoagulation with warfarin

Name 3 conditions that are associated with a high risk of developing DIC

Sepsis Ob complications Malignancy

Describe the pathophysiology of sickle cell anemia

Sickle cell disease is an inherited disorder that affects erythrocytes. Amino acid substitution (valine is substituted for glutamic acid) on the beta globulin chain alters RBC geometry. This affects RBC function: -Deoxygenation of HgbS leads to sickling -In severe cases, sickling causes the RBCs to clump together, which causes mechanical obstruction of the microvasculature in the vital organs and joints. This impairs tissue perfusion and causes intense pain -Sickled cells are more prone to hemolysis and removal by the spleen (lifespan = 12-17 days)

Presentation of hypocalcemia

Skeletal muscle cramps Nerve irritability- paresthesia and tetany Chvostek sign Laryngospasm Mental status changes- seizures Long QT interval

Where is vWF synthesized, and what is its function?

Synthesized by the vascular endothelium and megakaryocytes 2 functions Anchors PLT to the vessel wall at the site of vascular injury (PLT adhesion) Carries inactivated factor VIII in the plasma

What is anion gap, and what does it tell you?

The anion gap helps us determine the cause of the acidosis Anion ion gap = Major cations - Major anions Normal is 8-12 mEq/L Accumulation of acid = >14 = gap acidosis Loss of bicarb or ECF dilution = non-gap acidosis

What is the glycocalyx, and what factors disrupt it?

The endothelial glycocalyx forms a protective layer on the interior wall of the blood vessel. It is the gatekeeper that determines what can pass from the vessel into the interstitial space. It also contains anticoagulant properties. Disruption of the glycocalyx contributes to capillary leak. Accumulation of fluid and debris in the interstitial space reduces tissue oxygenation. Conditions that impair the integrity of the glycocalyx include: Sepsis Ischemia DM Major vascular surgery

Regarding the extrinsic pathway: -What activates it? -What lab tests measure it? -What drug inhibits it?

The extrinsic pathway is activated by vascular injury (tissue trauma liberates tissue factor from the subendothelium) Measured by PT and INR Inhibited by coumadin

Regarding the intrinsic pathway: -What activates it? -What lab tests measure it? -What drug inhibits it?

The intrinsic pathway is activated by blood injury or exposure to collagen Measured by PTT and ACT Inhibited by heparin

What are the 2 most important determinants of fluid transfer between capillaries and interstitial space?

The plasma is in direct contact with the interstitial fluid by way of pores in the capillaries. The movement of fluid between the intravascular space and interstitial space is determined by: Starling forces The glycocalyx

What drugs can be used to provide anticoagulation in a patient unable to receive heparin? How long must each be discontinued prior to surgery?

Thrombin inhibitors can be used to provide anticoagulation in patients unable to receive heparin Bivalirudin 2-3 hours Argatroban 4-6 hours Hirudin 8 hours

What is the difference between a hypotonic and hypertonic solution?

Tonicity compares the osmolarity of a solution relative to the osmolarity of the plasma.

What factors are in the intrinsic pathway?

VIII, IX, XI, XII If you can't buy the intrinsic pathway for 12$, you can buy it for 11.98

List all the antidotes for warfarin. -When should each be used?

Vitamin K (10-20mg PO, IM, IV) may be used to reverse warfarin for non-emergent, minor surgical procedures. It requires 4-8 hours to restore the concentration of vitamin K dependent clotting factors in the blood. Emergent or high-risk procedures require reversal with FFP 1-2 units, recombinant factor 7a, or prothrombin complex concentrate

What conditions can cause vitamin K deficiency?

Vitamin K is a fat-soluble vitamin that requires the presence of fat and bile for absorption. It is also manufactured by bacteria in the gut. Malabsorptive diseases, impaired GI flora, and decreased bile production can impair fat absorption and therefore create vitamin K deficiency

Describe the distribution of body water

Water represents 60% of TBW = 42L TBW can be divided into: ICF = 40% of TBW- 28L ECF 20% of TBW - 14L ECV can be further divided into Interstitial fluid = 16% of TBW- 11L Plasma fluid = 4% of TBW - 3L

Can a pregnant patient receive IV heparin?

Yes, it does not cross the placenta.

Pulmonary effects of alkalosis

decreased pulmonary vascular resistance

Presentation of hypercalcemia

nausea abdominal pain HTN psychosis mental status changes - seizures