Bleeding and Bruising - Disorders of Hemostasis - Differential Diagnosis Framework



== Quantitative or Qualitative defect in platelets == 



• Mucosal bleeding of the gums and gastrointestinal tract is more characteristic of a platelet disorder than of a coagulopathy.

• Bleeding gums can also arise from gingivitis or gingival leukemic infiltration.



== Deficiency or an inhibitor of a coagulation factor == 



NORMAL PT/NORMAL PTT:

• Von Willebrand’s disease

• Factor XIII deficiency

• Disorders of fibrinolysis

• Disorders of vascular integrity

Clotting cascade is intact - test for Von Willebrand disease:

• Von Willebrand factor Ag

• Von Willebrand factor activity (also called ristocetin cofactor activity)

• Factor VIII level



NORMAL PT/ABNORMAL PTT:

Abnormality in the intrinsic pathway.  Perform a PTT mixing study to distinguish abnormalities in the clotting factors (VIII, IX, and XI) vs. clotting factor inhibitors - factor VIII inhibitor and lupus anticoagulant.

Inherited:

• Deficiency of factor VIII, IX, or XI

• Deficiency of factor XII, prekallikrein, or HMW kininogen (not associated with a bleeding diathesis)

• Von Willebrand disease

Acquired:

• Heparin, dabigatran, argatroban, direct factor Xa inhibitors (variable)*

• Acquired inhibitor of factor VIII, IX, XI, or XII

• Acquired von Willebrand syndrome

• Lupus anticoagulant (more likely to be associated with thrombosis than bleeding)



ABNORMAL PT/NORMAL PTT:

Suggests an abnormality in the extrinsic pathway. If the PT remains prolonged after Vitamin K administration, evaluation of factor VII should be undertaken.

Inherited:

• Factor VII deficiency

Acquired:

• Mild vitamin K deficiency

• Liver disease

• Warfarin

• Acute DIC



ABNORMAL PT/ABNORMAL PTT:

Prolongation of the PT and the PTT suggests liver failure, disseminated intravascular coagulation, or defects in the common pathway to the intrinsic and extrinsic pathways. The appropriate evaluations to discern these causes are liver function tests (if not already performed), fibrinogen levels, and testing factor assays.

Inherited:

• Deficiency of prothrombin, fibrinogen, factor V, or factor X

• Combined factor deficiencies

Acquired:

• Liver disease

• Acute DIC

• Severe vitamin K deficiency

• Anticoagulants (warfarin, direct thrombin inhibitors, others)*

• Acquired inhibitor of prothrombin, fibrinogen, factor V, or factor X

• Amyloidosis-associated factor X deficiency

• Anticoagulant rodenticide poisoning



== Disruption in vascular integrity == 



• Vasculitis

• Amyloidosis

• Scurvy

Connective Tissue Disorders:

• Ehlers Danlos

Nutrition:

• Vitamin C



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