Definition
A.Bleeding disorders may occur as a result of abnormalities in platelet number or function, coagulation factors, fibrinolysis, and blood vessel integrity.
B.Deficiencies or inhibitors of clotting factors, whether acquired or inherited, can result in bleeding disorders.
Incidence
A.Bleeding disorders occur frequently in seriously ill patients, and causes may vary from prolonged global clotting tests or isolated thrombocytopenia to composite defects, such as consumption coagulopathies.
B.A prolongation of global clotting times, such as the prothrombin time (PT) or the activated partial thromboplastin time (aPTT), may be apparent in 14% to 28% of critically ill patients.
C.The incidence of a low platelet count (platelet count <150,000 per microliter) in an intensive care population is 35% to 44%. Platelet counts of less than 100,000 per microliter may be seen in another 30% to 50% of patients.
Pathogenesis
A.Hemostasis is the process of clot formation at the site of blood vessel injury. Abnormal bleeding is often a result of the absence or dysfunction of one or more of the elements needed in clot formation.
B.Most clotting factors are synthesized by the liver. A final step dependent on vitamin K is required for Factors II, VII, IX, and X, and procoagulant proteins C and S. Factor VIII, von Willebrand factor (vWF), and tissue plasminogen activator are produced in the endothelium, including that of the liver. The liver reticuloendothelial system is responsible for metabolizing most clotting factors and fibrin degradation products (FDPs).
C.Coagulation factor inhibitors are antibodies that neutralize a specific clotting factor’s function. Alloantibodies occur in patients with inherited factor deficiency. Autoantibodies arise in patients without an inherited factor deficiency. The most commonly inhibited factor is Factor VIII.
D.Low platelet counts in critically ill individuals are frequently the result of increased platelet turnover due to thrombin generation, platelet activation, and enhanced platelet-vessel wall interaction. Sepsis is a frequent cause for thrombocytopenia in seriously ill patients. The severity of sepsis may be correlated with the reduction in the platelet count.
E.Drug-induced thrombocytopenia has been associated with a variety of prescription and over-the-counter (OTC) medications including quinine and some sulfa-containing antibiotics. Antigen–antibody responses lead to the destruction of platelets.
F.Immune thrombocytopenic purpura (ITP) occurs as a result of antibody-induced destruction of platelets. Primary ITP can occur without any known risk factors while secondary ITP is a result of an acute or chronic underlying disorder, such as AIDS, systemic lupus erythematosus, lymphoma, or hepatitis C.
G.Thrombotic thrombocytopenic purpura (TTP) is a rare condition that manifests with a combination of low platelet count, hemolytic anemia, renal failure, neurological abnormalities, and fever. This rare disorder stems from introducing certain platelet aggregating substances into the circulation. In many cases this is triggered by a lack of an enzyme that breaks down vWF, causing platelet aggregation and adherence to vascular endothelium. While this condition may occur in otherwise healthy people, it is also found in individuals with autoimmune disorders, HIV infection, and pregnancy.
H.Disseminated intravascular coagulation (DIC) is a systemic process that can cause both thrombosis and hemorrhage. The processes associated with coagulation and fibrinolysis become abnormally activated within the vessels and promote ongoing coagulation and fibrinolysis. Consumption of platelets is associated with constant generation of thrombin. Microvascular thrombi, along with inflammation, may cause injury to the microvasculature, resulting in organ dysfunction. Consumption of platelets and low levels of other factors increase the risk for hemorrhagic complications, especially in perioperative patients or those undergoing other invasive procedures. Thrombin generation is triggered and promoted by a lack of thrombin-generating inhibitory mechanisms. Impaired fibrin degradation, due to elevated circulating levels of plasminogen activator inhibitor-type 1 (PAI-1), further promotes intravascular fibrin deposition. Patients with DIC have a low or decreasing platelet count, prolongation of coagulation tests, low plasma levels of coagulation factors and inhibitors, and increased markers of fibrin formation or degradation, including D-dimer or FDPs. No single diagnostic test is used to confirm DIC. The presence of a condition associated with DIC and a combination of laboratory tests are necessary to confirm the diagnosis.
I.Von Willebrand disease (VWD) is the most common form of inherited bleeding disorder, resulting from a deficiency or defect of vWF. Individuals with VWD have defects in both platelet function and the coagulation pathway.
J.Hemophilia A is the most common form of hemophilia, accounting for approximately 85% of hemophilia cases. Caused by an x-linked recessive gene, it affects males most often. Although it is a genetic disorder, a number of cases occur without a family history of bleeding. Deficiency or defects of Factor VIII are associated with excessive bleeding, most often occurring in soft tissue, joints, and the gastrointestinal (GI) tract. Bleeding may be spontaneous or associated with trauma.
Predisposing Factors
A.TTP.
B.Hemolytic-uremic syndrome.
C.Chemotherapy-induced microangiopathic.
D.Hemolytic anemia.
E.Severe malignant hypertension.
F.Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome of pregnancy.
G.Preeclampsia.
H.Retained products of conception.
I.Malignancy, especially leukemia.
J.Blood transfusion reaction.
K.Systemic infection.
L.Connective tissue disease.
M.Pancreatitis.
N.Liver disease.
O.Surgery or trauma.
P.Burns.
Q.Snake venom.
Subjective Data
A.Common complaints/symptoms.
1.Bruising.
2.Nose bleeds.
3.Bleeding gums.
4.Menorrhagia.
5.Weakness.
6.Fatigue.
7.Abdominal discomfort.
B.Common/typical scenario.
1.Other signs and symptoms.
a.Immediate bleeding after vessel injury is frequently associated with platelet disorders.
b.Large ecchymoses and large, diffusely spreading deep tissue hematomas are common with coagulation disorders.
c.Bleeding into synovial joints is characteristic of inherited coagulation disorders such as hemophilia.
d.Petechiae.
e.Oozing from venipuncture sites.
f.Uncontrolled postpartum bleeding.
C.Family and social history.
1.History of HIV infection and malignancy.
2.History of liver or kidney disease, or malabsorption that is often associated with bleeding.
3.Medication history including anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, antibiotics, alcohol, and dietary vitamins K and C.
4.Response to previous hemostatic challenges, including trauma, tooth extraction, pregnancy, surgery, sports, and menstruation.
5.Family history of bleeding disorders.
D.Review of systems.
1.Hematological: Ask about past bleeding problems, any history of anemia, bleeding after any type of surgical procedure or dental procedure, or any transfusions.
2.GI: Ask about dietary habits or antibiotic use which might contribute to vitamin K deficiency; ask about liver disease or black tarry stools.
3.Genitourinary: Ask about any kidney diseases or hematuria.
4.Endocrine.
a.Ask women about menses.
b.Ask about medications the patient is taking for other conditions.
5.Dermatological: Ask about bruising or ecchymosis.
Physical Examination
A.Signs of bleeding (e.g., petechiae, mucosal bleeding, soft tissue bleeding, ecchymoses). In hospitalized patients, bleeding from multiple sites can indicate DIC or TTP. Acute extensive mucocutaneous bleeding in a patient previously without symptoms should suggest ITP.
B.Organ enlargement.
C.Joint abnormalities.
D.Signs of systemic disease including fever and lympha-denopathy.
Diagnostic Tests
A.Complete blood count (CBC).
B.Bleeding time.
C.PT.
D.aPTT.
E.Platelet function analysis.
F.Examination of a peripheral blood smear.
The following may be required in the presence of abnormalities in screening tests described earlier.
G.Factor deficiencies and inhibitors.
H.Fibrinogen.
I.Fibrin and FDPs.
Differential Diagnosis
A.Anticoagulant overdose.
B.Acquired Factor VIII inhibitors.
C.Local surgical complications.
D.Physical abuse.
Evaluation and Management Plan
A.General plan.
1.Bleeding associated with deficiency of vitamin K can be treated with parenteral vitamin K. Normalization of clotting studies usually follows within several hours. Fresh frozen plasma may be needed in the event of hemorrhage or if emergency surgery is necessary.
2.Individuals with acute or chronic liver disease may require treatment of alterations in clotting functions, fibrinolytic systems, or platelet function. When multiple coagulation factors are involved, infusion of fresh frozen plasma is a preferred treatment. Additional treatments may include exchange transfusion and platelet infusion.
3.DIC treatment should be directed at reducing the burden of the underlying disease, controlling thrombosis, and preserving organ function. Controlling the underlying condition is necessary to reduce the stimulus for abnormal clotting and restoring a normal balance of clotting factors. The role of heparin is limited but has been effective when DIC is associated with retained products of conception and when acute promyelocytic leukemia is present. It is contraindicated when there is evidence of central nervous system (CNS), GI, or postoperative bleeding. Interventions for restoring the balance of coagulation factors and platelets include infusion of fresh frozen plasma, cryoprecipitate, and platelets.
4.Individuals with hemophilia should avoid trauma whenever possible. Medications that interfere with platelet function, including NSAIDs, should be avoided.