Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + TEST TAKING TIP Download Section PDF Listen +++ ++ Test Taking Tip Hematology requires lots of memorization. Important topics to look over include bleeding disorders and anticoagulants. These are basic questions you don't want to miss. + THE COAGULATION PATHWAY Download Section PDF Listen +++ +++ Sequence of the intrinsic pathway of coagulation: ++ Prekallikrein + HMW kininogen + Factor XII + exposed collagen → activates Factor XI → activates Factor IX, combines with Factor VIII → activates Factor X, combines with Factor V → converts prothrombin (Factor II) into thrombin. Thrombin converts fibrinogen into fibrin. ++ FIGURE 2-1. Schematic of the coagulation system. HMW, high molecular weight. (Reproduced from Brunicardi FC, Andersen DK, Billiar TR, et al. Schwartz's Principles of Surgery. 9th ed. http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) Graphic Jump LocationView Full Size||Download Slide (.ppt) +++ Sequence of the extrinsic pathway of coagulation: ++ Factor VII + tissue factor → activates Factor X, combines with Factor V → converts prothrombin into thrombin. Thrombin converts fibrinogen into fibrin. +++ Which factor is the convergence point and common to both the extrinsic and intrinsic pathways of coagulation? ++ Factor X +++ What does the prothrombin complex consist of? ++ Factor V, X, platelet factor 3, and prothrombin catalyzes the formation of thrombin +++ What function does thrombin have? ++ Activates factors V and VIII, activates platelets, and converts fibrinogen into fibrin and fibrin split products. It is instrumental in coagulation +++ Which factor has the shortest half-life? ++ Factor VII +++ What factor can be used to differentiate a consumptive coagulopathy from hepatocellular disease? ++ Factor VIII:C; consumptive coagulopathy will have reduced levels of all factors and hepatocellular disease will have reduced levels of all factors except factor VIII +++ Which factors are known as the labile factors (activity lost in stored blood)? ++ Factors V and VIII +++ What function does factor XIII have? ++ Cross-links fibrin +++ What does protein C do? ++ Degrades fibrinogen and Factors V and VIII (vitamin K dependent) +++ What does protein S do? ++ Acts as protein C cofactor (vitamin K dependent) +++ What does Von Willebrand factor (vWF) do? ++ Links collagen to the GpIb receptor on platelets +++ What is the function of antithrombin III? ++ Binds heparin, inhibits Factors IX, X, XI, and thrombin +++ Where does tissue plasminogen activator come from and what does it do? ++ Released from endothelium and it converts plasminogen into plasmin +++ What does plasmin do? ++ Degrades fibrinogen, fibrin, and Factors V and VIII +++ What is the natural inhibitor of plasmin called and where does it come from? ++ Alpha-2 antiplasmin; comes from the endothelium +++ What are the vitamin K–dependent factors? ++ Factors II, VII, IX, and X and proteins C and S +++ What function does tissue factor pathway inhibitor have? ++ Inhibits factor X + LABORATORY TESTS AND DATA Download Section PDF Listen +++ +++ PT measures the function of these factors: ++ Factors II, V, VII, and X and fibrinogen +++ What 2 factors are not measured by the PTT? ++ Factors VII and XIII +++ PTT measures the function of these factors: ++ Factors II, V, VIII, IX, X, XI, and XII and fibrinogen +++ What is the normal value for bleeding time and what does it imply? ++ Normal bleeding time ranges from 3 to 9 minutes and implies platelet counts >50,000/mL and normal platelet function +++ What test aids in detecting circulating anticoagulants, qualitative abnormalities of fibrin, inhibition of fibrin polymerization, and measures the clotting time of plasma? ++ Thrombin time +++ Patients bleeding after a large number of blood transfusions should be considered to have: ++ Dilutional thrombocytopenia (vs hemolytic transfusion reaction) +++ What factors are common to both the PT and PTT? ++ Factors II, V, and X and fibrinogen ++ FIGURE 2-2. Biology of hemostasis. The 4 physiologic processes that interrelate to limit blood loss from an injured vessel are illustrated and include vascular constriction, platelet plug formation, fibrin clot formation, and fibrinolysis. (Reproduced from Brunicardi FC, Andersen DK, Billiar TR, et al. Schwartz's Principles of Surgery. 9th ed. http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) Graphic Jump LocationView Full Size||Download Slide (.ppt) +++ How many hours must elapse after the last dose of IV heparin before the PT can be reliably measured? ++ Minimum of 5 hours +++ Sequence of physiologic reactions that mediate hemostasis following vascular injury? ++ Vasoconstriction Platelet activation/adherence/aggregation Thrombin generation + HYPERCOAGULABILITY DISORDERS Download Section PDF Listen +++ +++ What is Virchow triad? ++ Stasis, endothelial injury, and hypercoagulability +++ What is the most common cause of acquired hypercoagulability? ++ Smoking +++ What is the most common inherited hypercoagulable state? ++ Factor V Leiden +++ What is the treatment for hyperhomocysteinemia? ++ Vitamin B-12 and folate +++ Name the prothrombin gene defect causing spontaneous venous thrombosis. ++ Prothrombin gene defect G20210A + PLATELET FUNCTION AND DYSFUNCTION Download Section PDF Listen +++ +++ What is the normal life span of a platelet? ++ 7 to 10 days +++ Formation of a platelet plug requires these 2 electrolytes: ++ Calcium and magnesium ++ FIGURE 2-3. Schematic of platelet activation and thrombus function. ADP, adenosine diphosphate. (Reproduced from Brunicardi FC, Andersen DK, Billiar TR, et al. Schwartz's Principles of Surgery. 9th ed. http://www.accessmedicine.com. Copyright © The McGraw-Hill Companies, Inc. All rights reserved.) Graphic Jump LocationView Full Size||Download Slide (.ppt) +++ Platelet count needed before surgery: ++ >50,000/mL +++ Platelet count associated with spontaneous bleeding: ++ <20,000/mL +++ Platelet count when prophylactic platelet transfusions should be given: ++ <10,000/mL +++ Time to formation of a platelet plug is measured by this test: ++ Bleeding time +++ Inhibits platelet aggregation by inhibiting prostaglandin synthesis (PGG2, PGGH2) from arachidonic acid: ++ NSAIDs (ASA, ibuprofen, etc) +++ Uremia leads to a downregulation of: ++ GpIb, GpIIb/IIIA, and vWF +++ Initial treatment of choice for uremic coagulopathy: ++ Dialysis +++ Drug that can be given to help correct platelet dysfunction from uremia, bypass, or ASA: ++ Desmopressin (DDAVP) +++ DDAVP and conjugated estrogens stimulate the release of: ++ Factor VII and vWF + RED BLOOD CELL/BLOOD PRODUCTS Download Section PDF Listen +++ +++ Cause of microcytic anemia in a man or postmenopausal woman until proven otherwise: ++ Colon cancer +++ What is the normal life span of a red blood cell? ++ 120 days +++ The electrolyte most likely to fall after infusion of stored blood: ++ Ionized calcium (citrate in stored blood binds serum calcium) +++ How long can PRBCs be stored? ++ ~42 days or 6 weeks +++ Most common blood product to contain bacterial contamination: ++ Platelets +++ What type of bacteria is usually found in contaminated platelets? ++ Gram-positive organisms +++ Most common bacteria found with blood product contamination: ++ Gram-negative rods (Escherichia coli) +++ What types of infectious diseases can be transmitted by transfusion? ++ Hepatitis B and C, HIV, HTLV I and II, Chagas disease, malaria, and "theoretical risk" of Creutzfeldt-Jacob disease +++ True or False: Washed red blood cells can be given safely to patients who have had severe allergic/anaphylactic reactions to plasma. ++ True, because there are barely any plasma proteins in washed red blood cells. +++ The use of transfusion with leukocyte reduced packed red blood cells are justified in: ++ Patients with multiple reactions despite premedication with antipyretics, needing long-term platelet support, and transplant candidates in order to prevent formation of HLA antibodies. +++ What are the laboratory criteria for diagnosis of a hemolytic transfusion reaction? ++ Hemoglobinuria with free hemoglobin concentrations >5 mg/dL, serologic confirmation of incompatibility, and positive direct antiglobulin test results +++ Approximate formula to convert Hct into Hgb: ++ Hct/3 = Hgb +++ 1 U PRBC should increase the Hgb and Hct by: ++ 1 g/dL and Hct by ~3% to 4% +++ Which blood type is the universal donor? ++ O negative +++ What happens during a type and screen? ++ Patient's blood is screened for antibodies and blood type is determined. +++ What happens for a type and cross? ++ Recipient's serum is checked for preformed antibodies against donor's antigens in PRBC. +++ What fluid cannot be infused with PRBC and why? ++ Lactated Ringer's; calcium in LR may result in coagulation within the IV line. +++ What is the most common cause of transfusion hemolysis? ++ Clerical error leading to ABO incompatibility. +++ Symptoms of transfusion reaction: ++ Fever, chills, nausea, hypotension, lumbar/chest pain, abnormal bleeding, and pain at infusion site. +++ Treatment of transfusion hemolysis: ++ Stop transfusion; fluids; Lasix; alkalinize urine with bicarbonate; pressors as needed. + CLOTTING DISORDERS AND TREATMENT Download Section PDF Listen +++ +++ How long does it take for vitamin K to take effect? ++ 6 hours +++ How long do the effects of FFP last? ++ 6 hours +++ How long does it take for FFP to work? ++ Immediately +++ What does cryoprecipitate contain? ++ vWF, Factor VIII, and fibrinogen +++ What does FFP contain? ++ All factors including labile Factors V and VIII, AT-III, proteins C and S +++ What is the best method for detecting patients at risk for bleeding? ++ A complete history and physical examination +++ True or False: A normal circumcision rules out a bleeding disorder. ++ False. Newborns may not bleed at circumcision because of clotting factors from the mother (Factor VIII crosses the placenta). +++ What percentage of patients with a bleeding disorder is picked up by abnormal bleeding from tonsillectomy or tooth extraction? ++ 99% +++ What is the most common congenital bleeding disorder? ++ Von Willebrand disease +++ This factor is deficient in hemophilia A: ++ Factor VIII +++ Preoperative treatment for hemophilia A: ++ Factor VIII infusion to 100% normal preoperative levels +++ Coagulation study that is elevated in hemophilia A: ++ PTT +++ Factor deficient in hemophilia B: ++ Factor IX +++ Inheritance of hemophilia A and B: ++ Sex-linked recessive +++ What is the treatment for hemarthrosis in a patient with hemophilia A? ++ Initial therapy includes Factor VIII, joint rest, cold packs (3–5 days), and a compression dressing (3–5 days), followed by active range of motion exercised 24 hours after Factor VIII therapy. +++ How long does it take for desmopressin to reach its maximal procoagulant effect? ++ 1 to 2 hours +++ Deficiency in Von Willebrand disease: ++ vWF and factor VIII:C +++ Inheritance of Von Willebrand disease: ++ Autosomal dominant +++ Treatment of Von Willebrand disease: ++ DDAVP or cryoprecipitate +++ What type of Von Willebrand disease is desmopressin or DDAVP specifically contraindicated? ++ Type 2B +++ Name of syndrome for deficiency of factor XI? Treatment? ++ Rosenthal syndrome; plasma +++ What is the eponym for the deficiencies of Factors VII and X? Treatment? ++ Stuart-Prower deficiency; plasma +++ What receptor deficiency is found in Glanzmann thrombocytopenia? ++ GpIIb/IIIa receptor deficiency. The platelets cannot bind to each other. +++ What is the treatment for Glanzmann thrombocytopenia? ++ Platelets +++ What receptor deficiency is found in Bernard Soulier disease? ++ GpIb receptor deficiency. The platelets cannot bind to collagen +++ What is the treatment for Bernard Soulier disease? ++ Platelets +++ Mechanism by which DIC occurs: ++ Thromboplastic materials are introduced into the circulation that leads to activation of the coagulation system with protective or secondary fibrinolysis. +++ What is the most important component in the treatment of DIC? ++ Correcting the underlying cause +++ Examples of fast DIC: ++ Amniotic fluid embolus, placenta abruption, septic abortion, septicemia, massive tissue injury, incompatible blood transfusion, purpura fulminans +++ Examples of slow DIC: ++ Liver disease, Kasabach-Merritt syndrome, acute promyelocytic leukemia, dead fetus syndrome, transfusion of activated prothrombin complex concentrates, carcinomas +++ Postoperative patients with untreated polycythemia vera are at risk for: ++ Postoperative thrombosis, bleeding, combination of thrombosis and bleeding, or infection +++ What are the desired platelet counts and hematocrit in a patient with polycythemia vera before an elective operation? ++ Plt < 400,000/mL and Hct < 48% + ANTICOAGULATION Download Section PDF Listen +++ +++ Heparin binds to this protein for its anti-coagulation effects: ++ Anti-thrombin III; heparin-antithrombin III complex then binds Factor IX, X, and XI +++ What is the half-life of heparin? ++ 90 minutes +++ What is the dose of protamine to reverse 100 U or 1 mg of heparin? ++ 1 to 1.5 mg +++ What are signs seen in a protamine reaction? ++ Bradycardia, hypotension, and decreased heart function +++ Name the diagnosis: A patient is given Coumadin for a PE; 3 days later his skin sloughs off his arms and legs: ++ Warfarin-induced skin necrosis. +++ Reason that warfarin-induced skin necrosis occurs: ++ Proteins C and S have a shorter half-life than Factors II, VII, IX, and X. Coumadin leads to a decrease in proteins C and S before the other factors leading to a hypercoagulable state +++ Patients with this deficiency are at increased risk for warfarin-induced skin necrosis: ++ Protein C deficiency +++ Mechanisms where extracorporeal circulation may lead to bleeding? ++ Inadequate reversal of heparin, overadministration of protamine, or thrombocytopenia +++ Mechanism where extracorporeal circulation may lead to clotting? ++ Activation of Factor XII +++ What is the desired activated clotting time for routine anticoagulation? ++ 150 to 200 seconds +++ What is the desired activated clotting time for cardiopulmonary bypass? ++ 400 seconds +++ What surgical procedures require an INR < 1.2? ++ Neurosurgical procedures, operations on the prostate or eye, or blind needle aspiration +++ What INR is a contraindication to intramuscular injection? ++ INR > 1.5 +++ What are the absolute contraindications to the use of thrombolytics? ++ Recent CVA (<2 months), intracranial pathology, and active internal bleeding +++ What is Argatroban? ++ A synthetic direct thrombin inhibitor derived from L-arginine +++ What is Hirudin? ++ An irreversible direct thrombin inhibitor derived from leeches +++ What is Ancrod? ++ Malayan pit viper venom that stimulates tPA release +++ What is the length of anticoagulation treatment for first, second, or third episode of DVT? For significant PE? ++ Coumadin for 6 months, 1 year, and lifetime, respectively; lifetime anticoagulation for those who had a significant PE. +++ What are the indications for an IVC filter? ++ Patients who have undergone a pulmonary embolectomy; patients with documented PE while anticoagulated; patients with free-floating femoral, iliofemoral, IVC DVT; patients with contraindication to anticoagulation; patients at high risk for DVT (head injured/orthopedic injured on prolonged bed rest)