Clinical Laboratory - Hematology

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Laboratory Tests for the Diagnosis and Monitoring of Common Bleeding and Thrombotic Disorders

The standard preoperative workup includes:

  • Prothrombin time (PT)

  • Partial thromboplastin time (PTT)

  • Platelet count (part of CBC)

Additional tests may be added as the history and physical exam dictates. A bleeding time has been replaced by platelet function analysis (PFA). Specific coagulation factor assays are done in the workup of thrombotic or bleeding disorders.

Prothrombin Time (PT)

The PT is an in vitro measure of the "extrinsic" pathway of coagulation, stimulated by tissue thromboplastin. It primarily detects problems affecting the vitamin K dependent (liver synthesized) factors II, VII, IX, and X. The PT is affected initially by liver disease, coumadin therapy, or vitamin K deficiency.

Since factor VII has the shortest half-life of the coagulation factors, the PT is the first affected test in many cases.

Partial Thromboplastin Time (PTT)

The PTT is an in vitro measure of the "intrinsic" pathway of coagulation, stimulated by activated platelets and endothelial damage with release of Hagemann factor. It potentially measures factors II, V, VIII, IX, X, XI, XII. The PTT is affected initially by specific factor deficiencies, such as hemophilia, or Heparin therapy.

Severe liver disease, severe vitamin K deficiency, and prolonged coumadin therapy will eventually affect both the PT and PTT. Factor deficiencies of II, V, and X can potentially affect both pathways.


This test tends to be ordered to confirm a consumptive coagulopathy, such as DIC. Curiously, congenital afibrinogenemia (no detectable fibrinogen in either plasma or platelets) may be associated with infrequent, mild bleeding episodes.

Specific Factor Deficiencies

These tests are ordered only in specific circumstances to determine if an acquired or inherited factor deficiency is present. These patients are at increased risk for bleeding problems, and may have a history of exessive bleeding. The most often ordered are:

  • VWF: decreased with vonWillebrand disease

  • Factor VIII activity: reduced with hemophilia A

  • Factor IX: diminished with hemophilia B

Rare factor deficiencies include:

Factor XIII: stabilizes fibrin clots. Bleeding is first observed in the neonatal period. Patients may have poor wound healing, male infertility, abortion, and intracerebral hemorrhage.

Factor XII: abnormal contact activation pathway with Hageman factor. Causes a markedly prolonged PTT but no clinical bleeding.

Microangiopathic Hemolytic Anemias (MAHA)

Extensive consumption of multiple coagulation factors and elevated D-dimer can occur with MAHA. Forms of MAHA include disseminated intraascular coagulopathy (DIC) and thrombotic thrombocytopenic purpura (TTP), which may overlap with hemolytic uremic syndrome (HUS).

Mixing Study

The minimal level of a factor or factor activity for adequate hemostasis is about 25% of normal. Thus, one clue to factor deficiency is a mixing study in which patient plasma is mixed with an equal volume of normal plasma (1:1 ratio). If the problem corrects with mixing, then it is a factor deficiency. If the problem does not correct, then there is a factor inhibitor present, such as an antiphospholipid antibody.

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