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Overview of Coagulation Disorders


Michael B. Streiff

, MD, Johns Hopkins University School of Medicine

Reviewed/Revised Sep 2023

The major causes of acquired coagulation disorders are

Severe liver disease (eg, cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more , fulminant hepatitis Fulminant Hepatitis Fulminant hepatitis is a rare syndrome of rapid (usually within days or weeks), massive necrosis of liver parenchyma and a decrease in liver size (acute yellow atrophy); it usually occurs after... read more , acute fatty liver of pregnancy Fatty liver of pregnancy Hepatic disorders in pregnancy may be Unique to pregnancy Preexisting Coincident with pregnancy and possibly exacerbated by pregnancy Jaundice may result from nonobstetric or obstetric conditions. read more ) may disturb hemostasis Overview of Hemostasis Hemostasis, the arrest of bleeding from an injured blood vessel, requires the combined activity of Vascular factors Platelets Plasma coagulation factors Regulatory mechanisms counterbalance... read more by impairing clotting factor synthesis. Because all coagulation factors are made in the liver (by hepatocytes and hepatic sinusoidal 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

The most common hereditary coagulation disorders are

Testing for Coagulation Disorders

Patients in whom a coagulation disorder is suspected require laboratory evaluation beginning with

  • Prothrombin time (PT) and partial thromboplastin time (PTT)

  • Complete blood count (CBC) with platelet count

  • Peripheral blood smear

Results of these tests narrow the diagnostic possibilities and guide further testing.

Normal results

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 von Willebrand disease by measuring plasma von Willebrand factor (VWF) antigen, ristocetin cofactor activity (an indirect test of VWF function), 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 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 the CBC and peripheral blood smear demonstrate other cytopenias or immature white blood cells, a hematologic abnormality affecting multiple cell types should be suspected. Bone marrow aspiration and biopsy are then necessary for diagnosis.

Prolonged PTT with normal platelets and PT

A prolonged PTT with a normal platelet count 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 , and 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. In patients with normal factor VIII and factor IX levels, factor XI deficiency (hemophilia C, or Rosenthal disease) should also be considered. Factor XI deficiency is particularly common in patients with Ashkenazi Jewish ancestry.

Prolonged PT with normal platelets and PTT

A prolonged PT with a normal platelet count 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, in patients with early 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 in patients with incipient liver disease.

Prolonged PT and PTT with thrombocytopenia

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

A prolonged PT or PTT with a normal platelet count can occur with liver disease 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, direct oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban), or direct thrombin inhibitors (argatroban, bivalirudin—see table ).

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.

Drugs Mentioned In This Article

Drug Name Select Trade
Coumadin, Jantoven
Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin
Xarelto, Xarelto Granules, Xarelto Starter Pack
Angiomax, Bivalirudin
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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