VII. TEACHING POINTS

1. Inherited coagulopathies are not always recognized in childhood. They should be included in the differential diagnosis of any person with a bleeding disorder.


2. It is extremely important to obtain a complete history from patients with coagulation disorders.
   
   
   • The family history should also be explored in detail. If positive, the family history is very helpful in establishing a diagnosis of an inherited bleeding disorder.
   • A complete history of drugs and diet should also be obtained because both can alter hemostasis.
   
   
3. The coagulation system scheme shown below is useful to determine which clotting factors are measured, and by which of the two coagulation assays (aPTT and PT) that are in wide use. However, this schema is not representative of physiologic hemostasis.



• The activated partial thromboplastin time (aPTT) is prolonged by abnormalities of all the clotting factors with the exception of factor VII.
• The prothrombin time (PT) is prolonged by abnormalities of factors V, VII, X, prothrombin (factor II), and fibrinogen
• Factors II (prothrombin), VII, IX, and X are vitamin K dependent


4. The activated partial thromboplastin time (aPTT) and prothrombin time (PT) can be used to identify a specific clotting defect. Patients' test results may include any of the following:


• both tests normal
• aPTT prolonged and PT normal
• PT prolonged and aPTT normal
• both tests abnormal


5. An analysis of the aPTT and PT results taken together helps to further delineate the nature of the coagulation defect, as shown in the following table.
   

Interpretation of PT and aPTT
PT Long / aPTT Nl.	PT Nl. / aPTT Long	PT Long / aPTT Long
Low factor VII Mild dysfibrinogenemia	Low factor VIII, IX, XI, or XII Lupus anticoagulant Heparin therapy Low prekallikrein (PK) or high molecular weight kininogen (HMWK)	Low factor V or X Low fibrinogen or prothrombin High hematocrit (polycythemias) Vitamin K deficiency Warfarin therapy Liver disease Anticoagulants Disseminated Intravascular Coagulation (DIC) Massive transfusion
Adapted from Aggarwal & Alving, Blood Components, p5



6. von Willebrand factor (vWF) plays an important role in both platelet adherence and thrombus formation and coagulation.
   
   
   • The higher molecular weight multimers mediate platelet adhesion to the endothelial matrix.
   • vWF binds factor VIII to facilitate its export from endoplasmic reticulum and to stabilize its circulation in plasma (which rapidly degrades in the absence of vWF).
     
     
7. A von Willebrand factor antigen test is used for quantitative analysis of von Willebrand factor. The Ristocetin cofactor test can be used for qualitative analysis of von Willebrand factor. A collagen binding assay can also be used for the diagnosis of some subtypes of von Willebrand disease.


8. There are three major subtypes of von Willebrand disease. Type 1 is the most common and least severe.


9. It is important to identify the patient’s subtype of von Willebrand disease in order to choose appropriate therapy.

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