CHAPTER 2
Hematology
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
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.)
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
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.)
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?
1. Vasoconstriction
2. Platelet activation/adherence/aggregation
3. Thrombin generation
HYPERCOAGULABILITY DISORDERS
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
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.)
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
Cause of microcytic anemia in a man or postmenopausal woman until proven otherwise:
Colon cancer