Bleeding Disorders

Bleeding disorders

•          characterized clinically by abnormal bleeding

–         Spontaneous

–         Trauma or surgery

–        Systemic conditions that activate or damage endothelial cells

A normal hemostatic response involves blood vessel wall, platelets and clotting cascade

•          Excessive bleeding can result from

1. Increased fragility of vessels
2. Platelet deficiency or dysfunction
3. Derangement of coagulation
4. Combinations of these

Bleeding disorders 

•          Vessels wall abnormalities

•          Reduced platelet number

•          Defective platelet function 

•          Abnormalities in clotting factors

•          Disseminated intravascular coagulation

1.       Bleeding disorders caused by vessel wall abnormalities

•           severe vitamin C deficiency (scurvy)

•           systemic amyloidosis

•           chronic glucocorticoid use

•           inherited conditions affecting the connective tissues

•           infectious and hypersensitivity vasculitides

–         meningococcemia, infective endocarditis,  rickettsial diseases, typhoid, and Henoch-Schönlein purpura

•          Increased fragility of the vessels

•          Small hemorrhage (petechiae and purpura) in the skin or mucous membranes, particularly gingiva.

•          Platelet count, bleeding time and results of coagulation tests (PT, PTT) are usually normal

•          Bleeding rarely life threatening except some cases of hereditary telangiectasia

2.       Bleeding related to reduced platelet number (Thrombocytopenia)

•          Generalized bleeding

•          Normal platelet count: 150,000-300,000/ul

•          Thrombocytopenia: Count below 100,000/ul

•          Spontaneous bleeding: Count below 20,000/ul

•          Post traumatic bleeding: Count in the range of 20,000 to 50,000/ul

•          Prolonged BT, Normal PT and PTT

Causes of thrombocytopenia

•          Decreased production

–        Aplastic anemia

–        Leukemia

–        Drug induced- cytotoxic drugs, alcohol, thiazides

–        Ineffective megakaryopiesis- megaloblastic anemia, myelodysplastic syndrome

•          Decreased platelet survival

–        Immunologic destruction

•          Autoimmune- idiopathic thrombocytopenic purpura (ITP), SLE

•          Isoimmune- post transfusion

•          Drugs: heparin

•          Infections: infectious mononucleosis, HIV

–        Non-immunologic destruction

•          Disseminated intravascular coagulation

•          Thrombotic thrombocytopenic purputra

•          Microangiopathic hemolytic anemia

–        Sequestration

•          Hypersplenism

–        Dilutional : Massive transfusion  (no viable platelets in blood stored for longer than 24 hours)

3.       Bleeding disorders related to defective platelet functions

•          Congenital : Bernard-Soulier syndrome:                Defective adhesion of platelets to subendothelial matrix

•          Glanzmann’s thrombasthenia : Defective platelet aggregation

Acquired: aspirin, uremia

Clinical signs of inadequate platelet function

–         easy bruising

–         nosebleeds

–         excessive bleeding from minor trauma

–         menorrhagia

–         PT and PTT are normal, but bleeding time is prolonged

4.       Bleeding disorder related to abnormalities in clotting factor

•          All clotting factors except factor XII

•          Spontaneous bleeding (petechiate) uncommon

•          Large post-traumatic ecchymoses, hematoma, or prolonged bleeding after laceration, surgical procedure

•          Bleeding in GIT, Urinary tract, weight bearing joint common

•          Acquired

–        Vit K deficiency

–        Liver disease

–        Disseminated intravascular coagulation

•          Hereditary

–        Hemophilia A (factor VIII deficiency)

–        Christmas disease/hemophilia B (deficiency of factor IX)

Major disorders associated with DIC

1)      Obstetric complications

·         Abruptio placentae

·         Retained dead fetus

·         Septic abortion

·         Amniotic fluid embolism

·         Toxemia

2)      Infections

·         Gram negative sepsis

·         Meningococcemia

·         Histoplasmosis

·         Aspergillosis

·         Malaria

3)      Neoplasms

·         Carcinomas of pancreas, prostate, lung and stomach

·         Acute promyelocytic leukemia

4)      Massive tissue injury

·         Traumatic

·         Burns

·         Extensive surgery

5)      Miscellaneous: Acute intravascular hemolysis, snake bite, shock

Disseminated intravascular coagulation:  laboratory and clinical features related to both thrombocytopenia and coagulation factor deficiencies

•           Von Willebrand disease is a fairly common

–        Both platelet and (to a lesser degree) coagulation factor function are abnormal

•          Various tests used in the initial evaluation of patients with bleeding disorders are as follows:

–        Bleeding time. This represents the time taken for a standardized skin puncture to stop bleeding

–         2 to 9 minutes

–        abnormal when there is a defect in platelet numbers or function

•          Platelet counts :150 × 10³ to 450 × 10³ cells/mm³

•          Prothrombin time (PT)

–        This procedure tests the adequacy of the extrinsic and common coagulation pathways

–         It represents the time needed for plasma to clot in the presence of an exogenously added source of tissue thromboplastin (e.g., brain extract) and Ca²⁺ ions

–        A prolonged PT can result from a deficiency of factors V, VII, or X, prothrombin, or fibrinogen

•          Partial thromboplastin time (PTT)

–         intrinsic and common clotting pathways

–        In this test the time needed for the plasma to clot in the presence of kaolin, cephalin, and calcium is measured

–         Kaolin serves to activate the contact-dependent factor XII, and cephalin substitutes for platelet phospholipids

–         Prolongation of PTT can be caused by a deficiency of factors V, VIII, IX, X, XI, or XII or prothrombin or fibrinogen or an acquired inhibitor (typically an antibody) that interferes with the intrinsic pathway

•          Specialized tests

–         measurement of levels of specific clotting factors, fibrinogen, and fibrin split products

–         assessment of the presence of circulating anticoagulants

–         evaluation of platelet function