Overview of Coagulation Disorders
The major causes of acquired coagulation disorders are
Severe liver disease (eg, cirrhosis, fulminant hepatitis, acute fatty liver of pregnancy) may disturb hemostasis by impairing clotting factor synthesis. Because all coagulation factors are made in the liver (by hepatocytes and endothelial cells), both the prothrombin time (PT) and partial thromboplastin time (PTT) are prolonged in severe liver disorders. (PT results are typically reported as INR [international normalized ratio].) Occasionally, decompensated liver disease also causes excessive fibrinolysis and bleeding due to decreased hepatic synthesis of alpha 2-antiplasmin.
The most common hereditary disorder of hemostasis is
von Willebrand disease (VWD)
The most common hereditary coagulation disorders are
Patients in whom a coagulation disorder is suspected require laboratory evaluation beginning with
Results of these tests narrow the diagnostic possibilities and guide further testing.
Normal results on initial tests exclude many bleeding disorders. The main exceptions are
Von Willebrand disease is a common entity in which the associated deficiency of factor VIII is frequently insufficient to prolong the PTT. Patients who have normal initial test results, along with symptoms or signs of bleeding and a positive family history, should be tested for VWD by measuring plasma von Willebrand factor (VWF) antigen, ristocetin cofactor activity (an indirect test for large VWF multimers), VWF multimer pattern, and factor VIII levels.
Hereditary hemorrhagic telangiectasia (also called Osler-Weber-Rendu Syndrome) is a hereditary disorder of vascular malformation. People with this disorder have small red-to-violet telangiectatic lesions on the face, lips, oral and nasal mucosa, and tips of the fingers and toes. They may experience recurrent bleeding from the nasal mucosa and gastrointestinal tract and may have other potentially serious consequences of arteriovenous malformations.
If thrombocytopenia is present, the peripheral blood smear often suggests the cause.
If the smear is normal, patients should be tested for HIV infection. If the result of the HIV test is negative and the patient is not pregnant and has not taken a drug known to cause platelet destruction, then immune thrombocytopenia (ITP) is likely.
If the smear shows signs of hemolysis (fragmented red blood cells on smear, decreasing hemoglobin level), thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS) is suspected. "Classic" HUS occurs in patients with Shiga-like toxin-induced hemorrhagic colitis that occurs during infections with several Escherichia coli serotypes. An "atypical" form of HUS occurs uncommonly in individuals with congenital abnormalities of the alternative complement pathway. The Coombs test is negative in TTP and HUS.
If the CBC and peripheral blood smear demonstrate other cytopenias or abnormal white blood cells, a hematologic abnormality affecting multiple cell types is suspected. A bone marrow aspiration and biopsy are then necessary for diagnosis.
Prolonged PTT with normal platelets and PT suggests hemophilia A or B. Factor VIII and IX assays are indicated. Inhibitors that specifically prolong the PTT include an autoantibody against factor VIII and antibodies against protein-phospholipid complexes (lupus anticoagulant). Clinicians suspect one of these inhibitors when a prolonged PTT does not correct after 1:1 mixing with normal plasma.
Prolonged PT with normal platelets and PTT suggests factor VII deficiency. Congenital factor VII deficiency is rare; however, the short half-life of factor VII in plasma causes factor VII to decrease to low levels more rapidly than other vitamin K–dependent coagulation factors in patients beginning warfarin anticoagulation or in patients with incipient liver disease.
Prolonged PT and PTT with thrombocytopenia suggest DIC, especially in patients with obstetric complications, sepsis, cancer, or shock.
Confirmation is by finding elevated levels of D-dimer (or fibrin degradation products) and decreasing plasma fibrinogen levels on serial testing.
Prolonged PT or PTT with normal platelet count occurs with liver disease (except sometimes in portal hypertension, when the platelet count is reduced due to splenomegaly), vitamin K deficiency, or during anticoagulation with warfarin, unfractionated heparin, or a direct oral inhibitor of thrombin or factor Xa. Liver disease is suspected based on history or physical examination findings (eg, jaundice, hepatomegaly, splenomegaly, telangiectasia) and is confirmed by finding elevations of serum aminotransferases and bilirubin. Hepatitis testing is recommended.