Overview of Coagulation Disorders

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. Patients 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 Overview of Platelet Disorders Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more is present, the peripheral blood smear often suggests the cause.

If the smear is normal, patients should be tested for HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more . 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 Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more (ITP) is likely.

If the smear shows signs of hemolysis Diagnosis At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span... read more (fragmented red blood cells on smear, decreasing hemoglobin level), thrombotic thrombocytopenic purpura Thrombotic Thrombocytopenic Purpura (TTP) Thrombotic thrombocytopenic purpura (TTP) is an acute, fulminant disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. Other manifestations may include alterations... read more (TTP) or hemolytic-uremic syndrome Hemolytic-Uremic Syndrome (HUS) Hemolytic-uremic syndrome (HUS) is an acute, fulminant disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. HUS usually occurs in children... read more (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 Hemophilia Hemophilias are common hereditary bleeding disorders caused by deficiencies of either clotting factor VIII or IX. The extent of factor deficiency determines the probability and severity of bleeding... read more . 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 Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more , 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 Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more , when the platelet count is reduced due to splenic sequestration) or vitamin K deficiency Vitamin K Deficiency Vitamin K deficiency results from extremely inadequate intake or fat malabsorption. Risk of bleeding is increased by use of coumarin anticoagulants. Deficiency is particularly common among breastfed... read more , 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.