Bleeding Diathesis / Prolonged PTT - Approach

1) Clinical history:

a. Evaluation should include bleeding history, and history of “at-risk situations” (previous surgeries, childbirth etc.). 

b. Assess the type of bleeding: spontaneous or trauma/surgery related bleeding suggests moderate to severe deficiency in factors VIII or IX (rarely others); mucosal bleeding is more suggestive of underlying platelet disorders or VWD (disorders of primary hemostasis)

2) General screening tests include a platelet count, bleeding time, PT, aPTT and thrombin time (TT)

1. Bleeding time (BT): measure of plt interaction with blood vessels; prolonged in thrombocytopenia, qualitative plt defects (uremia) and VWD (can also use the Platelet Function Analyser, which is more sensitive than BT)
2. Prothrombin Time (PT): measure the production of fibrin via the extrinsic pathway and final common pathway—involves TF, FVII, factor X,V, prothrombin (FII) and fibrinogen.  Bypasses the intrinsic pathway.  Factors VII, X and PT are vit-K dept, so altered by warfarin
3. Activated partial thromboplastin time (aPTT): measures the intrinsic and common pathways—sensitive to inhibitors (ie. heparin) and deficiencies of ALL coagulation factors except VII and XIII. Less sensitive than the PT for deficiencies of the common pathway (X, V, prothrombin and fibrinogen). 
4. Thrombin time (TT) and reptilase time (RT): measure the conversion of fibrinogen to fibrin and formation in initial clot by thrombin and reptilase (can be caused by hypofibrinogenemia or increased fibrin split products, also useful for determining if heparin is present, which prolongs TT but not RT)

3) Prolonged PTT with a normal PT:

a. Due to disorders in the intrinsic pathway of coagulation

b. Inherited disorders include deficiencies of factors VIII (hemophilia A, von Willebrand disease), IX (hemophilia B), and XI OR

c.  Acquired inhibitors to Factors XI, IX or VIII, antiphospholipid AB or heparin use

d. Approach to prolonged PTT

I. Repeat blood draw from peripheral vein (ensure no heparin contamination); can add protamine or Heparsorb in the lab, if 2/2 heparin, will correct

II. Check a thrombin time and reptilase time (if TT is prolonged and reptiplase time normal, heparin is likely present)

III. Perform an inhibitor screen (mixing study): pt plasma is mixed with normal plasma and aPTT is rechecked after 1-2 hrs. Correction suggests a factor deficiency or VWD; lack of correction suggests a factor inhibitor (does not specify which factor is inhibited). Next step is to add phospholipid, if the PTT now corrects, this suggests the presence of antiphospholipid ABs

IV. If the aPTT does not correct with the above, check a Bethesda assay: checks for Factor VIII inhibitor and quantifies the AB titer.  The assay involves serial dilutions of pt plasma while checking Factor VIII activity; once FVIII activity reaches 50%, this is called one Bethesda units(BU) (the stronger the inhibitor, more dilution required)

(Victoria Kelly MD, 12/4/10)