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Excessive Bleeding


Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Mar 2020| Content last modified Mar 2020
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Unusual or excessive bleeding may be indicated by several different signs and symptoms. Patients may present with unexplained nosebleeds (epistaxis), excessive or prolonged menstrual blood flow (menorrhagia), or prolonged bleeding after minor cuts, tooth brushing or flossing, or trauma. Other patients may have unexplained skin lesions, including petechiae (small intradermal or mucosal hemorrhages), purpura (areas of mucosal or skin hemorrhage larger than petechiae), ecchymoses (bruises), or telangiectasias (dilated small vessels visible on skin or mucosa). Some critically ill patients may suddenly bleed from vascular punctures or skin lesions and have severe hemorrhage from these sites or from the gastrointestinal or genitourinary tract. In some patients, the first sign is a laboratory test abnormality suggesting the susceptibility to excessive bleeding that is found incidentally.

Etiology of Excessive Bleeding

Excessive bleeding can result from several mechanisms (see table Some Causes of Excessive Bleeding), including the following:

Platelet disorders may involve: an abnormal number of platelets (typically too few platelets, although an extremely elevated platelet count may be associated with excessive bleeding): defective platelet function, often due to drugs such as aspirin, P2Y12 inhibitors (eg, clopidogrel): or nonsteroidal anti-inflammatory drugs (NSAIDs), or both an abnormal number and defective function of platelets. Coagulation disorders may be acquired or hereditary.

Overall, the most common causes of excessive bleeding include

  • Excessive anticoagulation, as with warfarin, heparin, or a direct oral anticoagulant (eg, apixaban, edoxaban, rivaroxaban)

  • Liver disease (inadequate production of coagulation factors)


Some Causes of Excessive Bleeding



Platelet disorders

Decreased number of platelets (quantitative disorder)

Inadequate production (eg, in leukemias, aplastic anemia, and some myelodysplastic syndromes)

Splenic sequestration (eg, in cirrhosis with congestive splenomegaly)

Drug-induced destruction (eg, by heparin, quinidine, quinine, sulfonamides, sulfonylureas, or rifampin)

Increased number of platelets (quantitative disorder)

Essential thrombocythemia (thrombosis may be more common than bleeding)

Inadequate platelet function (qualitative disorder)

Von Willebrand disease (inadequate VWF-mediated platelet adhesion)

Drug-induced dysfunction (eg, by aspirin, the P2Y12 inhibitors [cangrelor, clopidogrel, prasugrel, ticagrelor], or NSAIDs)

Systemic disorders (uremia; occasionally, myeloproliferative disorders, myelodysplastic syndromes, multiple myeloma)

Coagulation disorders


Liver disease

Anticoagulation with warfarin, heparin or the direct oral inhibitors of thrombin or factor Xa (eg, apixaban, edoxaban, rivaroxaban)



Hemophilia A (factor VIII deficiency)

Hemophilia B (factor IX deficiency)

Vascular disorders



Connective tissue disorders (eg, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome)

DIC = disseminated intravascular coagulation; NSAIDs = nonsteroidal anti-inflammatory drugs; VWF = von Willebrand factor.

Evaluation of Excessive Bleeding


History of present illness should determine the bleeding sites, the amount and duration of bleeding, and the relationship of bleeding to any possible precipitating events.

Review of systems should specifically query about bleeding from sites other than those volunteered (eg, patients complaining of easy bruising should be questioned about frequent nosebleeds, gum bleeding while tooth brushing, melena, hemoptysis, blood in stool or urine). Patients should be asked about symptoms of possible causes, including abdominal pain and diarrhea (gastrointestinal illness); joint pain (connective tissue disorders); and amenorrhea plus morning sickness (pregnancy).

Past medical history should seek known systemic conditions associated with defects in platelets or coagulation, particularly

Drug history should be reviewed, particularly use of heparin, warfarin, P2Y12 inhibitors, direct oral inhibitors of thrombin or factor Xa (eg, apixaban, edoxaban, rivaroxaban), aspirin, and NSAIDs. Patients who are taking warfarin also should be questioned about intake of other drugs and foods (including herbal supplements) that impair the metabolism of warfarin and thus increase its anticoagulant effect.

Physical examination

Vital signs and general appearance can indicate hypovolemia (tachycardia, hypotension, pallor, diaphoresis) or infection (fever, tachycardia, hypotension with sepsis).

The skin and mucous membranes (nose, mouth, vagina) are examined for petechiae, purpura, and telangiectasias. Gastrointestinal bleeding can often be identified by digital rectal examination. Signs of bleeding in deeper tissues may include tenderness during movement and local swelling, muscle hematomas, and, for intracranial bleeding, confusion, stiff neck, focal neurologic abnormalities, or a combination of these findings.

Characteristic findings of alcohol abuse or liver disease are ascites, splenomegaly (secondary to portal hypertension), and jaundice.

Red flags

The following findings are of particular concern:

Interpretation of findings

Bleeding in a patient taking warfarin is especially likely if there has been a recent increase in dose or the addition of a drug or food that may interfere with warfarin inactivation. Telangiectasias on the face, lips, oral or nasal mucosa, and tips of the fingers and toes in a patient with a positive family history of excessive bleeding is likely to indicate hereditary hemorrhagic telangiectasia.

Bleeding from superficial sites, including skin and mucous membranes, suggests a quantitative or qualitative defect in platelets or a defect in blood vessels (eg, amyloidosis).

Bleeding into deep tissues (eg, hemarthroses, muscle hematomas, retroperitoneal hemorrhage) suggests a defect in coagulation (coagulopathy).

A family history of excessive bleeding suggests an inherited coagulopathy (eg, hemophilia), a qualitative platelet disorder, a type of von Willebrand disease (VWD), or hereditary hemorrhagic telangiectasia. Absence of a known family history does not, however, unequivocally exclude an inherited disorder of hemostasis.

Bleeding in a patient who is pregnant or has recently delivered, who is in shock, or who has a serious infection suggests disseminated intravascular coagulation (DIC).

Bloody diarrhea and thrombocytopenia in a patient with fever and gastrointestinal symptoms suggest the hemolytic-uremic syndrome (HUS), which is often associated with infection by Escherichia coli O157:H7 (or other Shiga-like toxin-producing type of E. coli ).

In a child, a palpable, purpuric rash on the extensor surfaces of the extremities suggests immunoglobulin A–associated vasculitis, particularly if accompanied by fever, polyarthralgia, or gastrointestinal symptoms.

Patients with known alcohol abuse or liver disease may have coagulopathy, splenomegaly, or thrombocytopenia.

Patients with a history of IV drug abuse or unprotected sexual exposure may have HIV infection.


Most patients require laboratory evaluation (see table Laboratory Tests of Hemostasis by Phase). The initial tests are

  • Complete blood count (CBC) with platelet count

  • Peripheral blood smear

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

Screening tests evaluate the components of hemostasis, including the number of circulating platelets and the plasma coagulation pathways (see figure Pathways in blood coagulation). The most common screening tests for bleeding disorders are the platelet count, PT, and PTT. If results are abnormal, a specific test can usually pinpoint the defect. Determination of the level of fibrin degradation products measures in vivo activation of fibrinolysis (usually secondary to excessive coagulation in DIC).

Prothrombin time (PT) screens for abnormalities in the extrinsic and common pathways of coagulation (plasma factors VII, X, V, prothrombin [II], and fibrinogen). The PT is reported as the international normalized ratio (INR), which reflects the ratio of the patient’s PT to the laboratory’s control value; the INR controls for differences in reagents among different laboratories. Because commercial reagents and instrumentation vary widely, each laboratory determines its own normal range for PT and PTT; a typical normal range for the PT is between 10 and 13 seconds. An INR > 1.5 or a PT 3 seconds longer than a laboratory’s normal control value is usually abnormal and requires further evaluation. The INR is valuable in screening for abnormal coagulation in various acquired conditions (eg, vitamin K deficiency, liver disease, DIC). It is also used to monitor therapy with the oral vitamin K antagonist, warfarin.

Partial thromboplastin time (PTT) screens plasma for abnormalities in factors of the intrinsic and common pathways (prekallikrein; high molecular weight kininogen; factors XII, XI, IX, VIII, X, and V; prothrombin [II]; fibrinogen). The PTT tests for deficiencies of all clotting factors except factor VII (measured by the PT) and factor XIII (measured by a factor XIII assay). A typical normal range is 28 to 34 seconds. A normal result indicates that at least 30% of all coagulation factors in the pathway are present in the tested plasma. Heparin prolongs the PTT, and the PTT is often used to monitor heparin therapy. Inhibitors that prolong the PTT include an autoantibody against factor VIII (see also Hemophilia and Coagulation Disorders Caused by Circulating Anticoagulants) and the lupus anticoagulant. The latter is an antibody against protein-phospholipid complexes that is found in the plasma of patients with systemic lupus erythematosus and other autoimmune disorders (see also Thrombotic Disorders).

Prolongation of PT or PTT may reflect

  • Clotting factor deficiency

  • Presence of an inhibitor of a component of the coagulation pathway (including the presence in circulation of a direct oral anticoagulant inhibiting thrombin or factor Xa)

The PT and PTT do not become prolonged until one or more of the clotting factors tested are about 70% deficient. For determining whether prolongation reflects a deficiency of one or more clotting factor or the presence of an inhibitor, the test is repeated after mixing the patient’s plasma with normal plasma in a 1:1 ratio. Because this mixture contains at least 50% of normal levels of all coagulation factors, failure of the mixture to correct almost completely the prolongation suggests the presence of an inhibitor in patient plasma.

The bleeding time test is not sufficiently reproducible to be reliable for clinical decision-making.


Laboratory Tests of Hemostasis by Phase



Formation of initial platelet plugs

Platelet count

Quantifies platelet number

Platelet aggregation

Evaluates adequacy of platelet responsiveness to physiologic stimuli that activate platelets (eg, collagen, ADP, arachidonic acid)

Detects abnormal patterns in hereditary or acquired platelet functional disorders

VWF antigen

Measures total concentration of plasma VWF protein

VWF multimer composition

Evaluates distribution of VWF multimers in plasma (eg, large multimers are missing in type 2 variants of VWD)

Ristocetin agglutination

Screens for the presence of large multimers of VWF in patient platelet-rich plasma (often done as part of routine laboratory evaluation for VWD)

Ristocetin cofactor activity

Quantifies large multimers of VWF in patient plasma using formalin-fixed test platelets

Formation of fibrin


Screens for the factors in extrinsic and common pathways (factors VII, X, and V; prothrombin [II]; and fibrinogen)


Screens for the factors in intrinsic and common pathways (prekallikrein; high molecular weight kininogen; factors XII, XI, IX, VIII, X, and V; prothrombin II]; and fibrinogen)

Specific functional assays for coagulation factors

Determines activity of the specific coagulant factor tested as a percentage of normal

Thrombin time

Evaluates the last step of coagulation (thrombin cleavage of fibrinogen to fibrin)

Is prolonged by heparin activation of antithrombin and in conditions resulting in qualitative fibrinogen abnormalities or hypofibrinogenemia

Reptilase time

Reptilase (a snake venom) also activates fibrinogen to fibrin.

If it is normal and thrombin time is prolonged, provides presumptive evidence that a plasma sample contains heparin (eg, residual heparin after extracorporeal bypass or in a sample drawn from an IV line kept open with heparin flushes) because reptilase time is not affected by heparin activation of antithrombin

Fibrinogen level

Quantifies plasma fibrinogen, which is increased in acute phase reactions (to infection and inflammation) and decreased in severe liver disease and severe DIC


Clot stability during 24-hour incubation in saline and in 5M urea

Lysis of clots occurs in saline if fibrinolytic activity is excessive or in 5M urea if factor XIII is deficient

Should be done in patients with defective wound healing or frequent miscarriages

Plasminogen activity

Quantifies plasma plasminogen, which is decreased in patients with congenital early-onset venous thromboembolism (rare)


Quantifies plasma level of this fibrinolysis inhibitor, which can be reduced in patients with increased fibrinolysis and excessive bleeding (rare)

Serum fibrinogen and fibrin degradation products

Screens for DIC

Increased levels are produced if plasmin cleaves fibrinogen or fibrin in vivo (eg, in DIC)

Superseded by plasma D-dimer assay

Plasma D-dimer

Is measured with a monoclonal antibody latex agglutination test or with an ELISA

If high, indicates that thrombin has been generated in vivo with resultant generation of fibrin, activation of the cross-linking enzyme factor XIII, and secondary fibrinolysis

Has the practical advantage that it can be done on citrate-containing plasma and thus, unlike the test for serum fibrin degradation products, does not require blood clotting in a special tube to prepare serum free of residual fibrinogen

Is useful in the diagnosis of DIC and in vivo thrombosis (eg, deep venous thrombosis, pulmonary embolism)

ADP = adenosine diphosphate; DIC = disseminated intravascular coagulation; ELISA = enzyme-linked immunosorbent assay; VWD = von Willebrand disease; VWF = von Willebrand factor.

Normal results on initial tests exclude many bleeding disorders. The main exceptions are VWD and hereditary hemorrhagic telangiectasia. VWD is a common entity in which the associated modest 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.

If thrombocytopenia is present, the peripheral blood smear often suggests the cause (see table Peripheral Blood Findings in Thrombocytopenic Disorders). If the smear shows no evidence of other abnormalities, 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 is likely. If there are signs of hemolysis (fragmented red blood cells on smear, decreasing hemoglobin level), DIC, thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) should be suspected, although sometimes other hemolytic disorders can cause these findings. HUS occurs in patients with hemorrhagic colitis. 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 should be suspected, and a bone marrow aspiration and biopsy are 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. Major sites of coagulation protein production include endothelial cells, including those lining liver sinusoids. Liver sinusoidal endothelial cells are often damaged in various liver disorders.

Prolonged PT and PTT with thrombocytopenia suggest DIC, especially in association with obstetric complications, sepsis, cancer, or shock. Confirmation is by finding elevated levels of D-dimers (or fibrin degradation products) and decreasing plasma fibrinogen levels on serial testing.

Prolonged PT or PTT with a normal platelet count occurs with liver disease or vitamin K deficiency or during anticoagulation with warfarin, unfractionated heparin, or the direct oral anticoagulants that inhibit thrombin or factor Xa. Liver disease is suspected based on history and is confirmed by finding elevations of serum aminotransferases and bilirubin; hepatitis testing is recommended.

Imaging tests are often required to detect occult bleeding in patients with bleeding disorders. For example, head CT should be done in patients with severe headaches, head injuries, or impairment of consciousness. Abdominal CT is needed in patients with abdominal pain or other findings compatible with intraperitoneal or retroperitoneal hemorrhage.

Treatment of Excessive Bleeding

  • Treat underlying disorder

Treatment is directed at the underlying disorder. In addition, hypovolemia should be corrected. For immediate treatment of bleeding due to a coagulopathy that has not yet been diagnosed, fresh frozen plasma, which contains all coagulation factors, should be infused pending definitive evaluation.

Key Points about Excessive Bleeding

  • Disseminated intravascular coagulation should be suspected in patients with sepsis, shock, or complications of pregnancy or delivery.

  • Mild platelet dysfunction caused by aspirin, P2Y12 inhibitors, or nonsteroidal anti-inflammatory drugs is common.

  • Easy bruising with no other clinical manifestations and normal laboratory test results is often benign.

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