Disorders of Primary Hemostasis (1).pdf

Disorders of Primary Hemostasis Clinical Hematology 2 - Lecture Kathleen Mae B. Dayoha, RMT, MBA Basic Terminology for Clinical Findings in Bleeding Disorders Basic Terminology for Clinical Findings in Bleeding Disorders 1. Petechiae Purplish red, pinpoint hemorrhagic spots, less than 3...

Disorders of Primary Hemostasis Clinical Hematology 2 - Lecture Kathleen Mae B. Dayoha, RMT, MBA Basic Terminology for Clinical Findings in Bleeding Disorders Basic Terminology for Clinical Findings in Bleeding Disorders 1. Petechiae Purplish red, pinpoint hemorrhagic spots, less than 3 mm in diameter, in the skin caused by loss of capillary ability to withstand normal blood pressure and trauma. Characteristic of abnormalities of platelets and blood vessels and usually are not seen in coagulation factor disorders. 2. Purpura A general term referring to all bruises from petechiae to ecchymoses. These are red areas in the skin (>3mm but less than 1 cm) that eventually turn purple then brownish yellow, caused by hemorrhage of blood into small areas of skin, mucous membranes and other tissues. Basic Terminology for Clinical Findings in Bleeding Disorders 3. Ecchymosis A form of purpura larger than 1 cm in diameter, in which blood escapes into large areas of skin or mucous membranes but not into deep tissue; commonly from a blood vessel larger than a capillary. They are red or purple when rst formed and become yellowish green as they heal. 4. Epistaxis Nosebleed fi Basic Terminology for Clinical Findings in Bleeding Disorders 5. Hemarthrosis Leakage of blood into a joint cavity 6. Hematemesis Vomiting of blood 7. Hematoma A blue or purple, raised or swelling area in the organ or tissues caused by blood leaking from an opening in a vessel and collecting beneath intact skin. Basic Terminology for Clinical Findings in Bleeding Disorders 8. Hematuria Intact red cells in the urine 9. Hemoglobinuria Refers to hemoglobin in the urine 10.Hemoptysis Expectoration of blood secondary to hemorrhage in the larynx, trachea, bronchi, or lungs Basic Terminology for Clinical Findings in Bleeding Disorders 11.Melena Stool containing dark red or black blood 12.Menorrhagia Excessive menstrual bleeding  Screening Tests for Defects of Primary Hemostasis Platelet Count Bleeding Time PT/APTT Vascular Disorders Thrombocytopenia Platelet Dysfunction Bleeding Disorders caused by Vascular Defects Bleeding Disorders caused by Vascular Defects Characterized by non-thrombocytopenia purpura Platelet count and screening tests for coagulation factors are usually normal.  Bleeding Disorders caused by Vascular Defects I. Connective Tissue Defects A. Inherited 1. Ehlers-Danlos Autosomal dominant Physical Findings: Hyper extensible joints & hyperplastic skin; connective tissue of the skin, vasculature, and bones is adversely a ected, causing a lack of structural support in these tissues and great tissue fragility Large skin ecchymosis & hematomas, bleeding from gums, excessive postpartum bleeding, GI bleeding, easy bruisability. Defect: peptidase enzyme de ciency (converts pro collagen to collagen) Lab ndings: Increased/prolonged bleeding time fi fi ff  Bleeding Disorders caused by Vascular Defects I. Connective Tissue Defects A. Inherited 2. Pseudoxanthoma elasticum Rare; autosomal recessive Connective tissue elastic bers in small arteries are calci ed and structurally abnormal Subarachnoid and GI bleeding are the most common cause of death Lab ndings: not signi cant fi fi fi fi Bleeding Disorders caused by Vascular Defects I. Connective Tissue Defects A. Inherited 3. Marfan syndrome Autosomal dominant; carried by Fibrillin-1 (FBN-1) gene Blood vessels has decreased strength and elasticity Marked by long limbs, dislocated lenses & aortic root dilation May also a ect the lungs, dural sac around the spinal cord and the hard palate Lab Findings: Increased/prolonged bleeding time. ff Bleeding Disorders caused by Vascular Defects I. Connective Tissue Defects B. Acquired 1. Scurvy Vitamin C is a cofactor for the enzymes required for the conversion of pro collagen to collagen, which is necessary to maintain the structural integrity of blood vessels. Physical nding includes gingival bleeding and hemorrhage into subcutaneous tissues and muscles, petechiae on thighs and buttocks, particularly around the hair follicles. Large hemorrhagic areas may develop below the eyes. Lab Findings: Anemia Decreased Vitamin C level in plasma (Ref range: 0.5 -1.0 mg/dL) Positive tourniquet test fi Bleeding Disorders caused by Vascular Defects I. Connective Tissue Defects B. Acquired 2. Senile Purpura Acquired and chronic disorder of the elderly due to the degeneration of collagen, elastin and subcutaneous fat due to the aging process Red to purple ecchymotic areas on the forearm and on the back of the hands, and neck which retains a permanent brownish color, possible due to hemoglobin that is not properly removed by the aging macrophage system. Bleeding Disorders caused by Vascular Defects I. Connective Tissue Defects B. Acquired 3. Cushing Syndrome and Corticosteroid Therapy Excess glucorticosteroids result in excessive breakdown of collagen, thin, fragile skin, vessel wall fragility, and bruising. Small blood vessels can be mechanically broken and bleed into the skin. Bleeding Disorders caused by Vascular Defects II. Altered Vessel Wall Structure A. Inherited 1. Hereditary Hemorrhagic Telangiectasia Characterized by the presence of skin lesions due to thin, dilated vessels that may bleed spontaneously or from minor trauma. They appear most commonly on the face, lips, tongue, mucous membranes of the mouth and the nose, the ears, conjuctivae, and the palms of the hands and soles of the feet. The telangiectasia is permanent. Due to bleeding tendencies, anemia may develop from iron de ciency. All tests for coagulation are normal. fi Bleeding Disorders caused by Vascular Defects II. Altered Vessel Wall Structure A. Inherited 2. Congenital hemangiomata (Kasabach - Merritt Syndrome) A disorder associated with tumors composed of vessels that commonly swell and bleed at the surface. Formation of brin clots, platelet consumption, and red cell destruction secondary to vascular obstruction occur at the site of the tumor. The tumors range in size from small to enormous lesions that protrude from the skin surface. They generally require surgical removal. fi Bleeding Disorders caused by Vascular Defects II. Altered Vessel Wall Structure B. Acquired 1. Diabetes mellitus Capillary basement membrane may thicken, blocking the normal ow of blood most often a ecting capillaries of the renal glomeruli, and the retina. 2. Amyloidosis Deposition of amyloid in the blood vessels causes various degrees of vessel fragility resulting in the formation of purpora at the skin surface. ff fl  Bleeding Disorders caused by Vascular Defects III. Endothelial damage/Vasculitis In ammation of the small blood vessels usually occurring when immune complexes attach to endothelial cells or the underlying sub endothelial structures and activate complement. 1. Autoimmune Vascular purpura a. Drug-induced b. Allergic purpura 2. Henoch- Schönlein Purpura A type of allergic purpura characterized by abdominal pain due to GIT hemorrhage, joint pain esp of the knee, ankles, and wrists. 3. Infectious purpura fl  Bleeding Disorders caused by Vascular Defects IV. Miscellaneous Causes of Purpura 1. Mechanical Purpura Increased pressure within the lumen of capillaries after intense exercise, coughing spasms, or epileptic seizures can cause petechial hemorrhages in the skin. 2. Arti cially induced purpura Bruises resulting from accidents or abuse, overuse of anticoagulant drugs or placing negative pressure on the skin. 3. Easy bruising syndrome (purpura simplex) A benign condition that commonly occurs in women. fi Bleeding Disorders caused by Vascular Defects IV. Miscellaneous Causes of Purpura 4. Purpura Fulminans A severe type of purpura seen in newborns and to others associated with abnormalities of certain clotting factors or inhibitors and in some patients under therapy for thrombotic conditions wherein thrombi forms in the capillaries supplying blood to the skin and subcutaneous tissues leading to necrosis and possibly death. 5. Psychogenic Purpura Severe recurrent erythema and ecchymosis, often accompanied by pain and swelling associated with psychiatric illness. Coagulations tests are normal and there is no evidence of underlying medical illness. Quantitative & Qualitative Platelet Disorders Definition of Terms 1. Thrombocytopenia Decreased platelet count below 100x10^9/L 2. Thrombocytosis Increased platelet count of more than 450x10^9/L 3. Thrombocythemia Fixed increase in circulating platelets associated with myeloproliferative disease 4. Thrombasthenia Functionally abnormal platelets (no brinogen receptors); normal count 5. Thrombocytopathia / thrombocytopathy Functionally abnormal platelets due to defective platelet factor 3 fi  Causes of Thrombocytopenia Impaired or Decreased Increased Platelet Destruction Production Non-immune Congenital Immune Infection Drug-induced Radiation Drugs Disorders Related to Distribution Ine ective Thrombopoiesis or Dilution Myelophthisis ff Changes in platelet count may be observed in the following 1. Platelet count is 10-20% lower in healthy West Indians and Africans than Europeans living in the same environment 2. 20% higher in women but a decrease may occur during menstruation 3. Higher in the 1st year of birth than adults 4. Vigorous exercise (30-40% increase) 5. Higher after epinephrine infusion 6. Higher in smokers 7. Higher/Increased in obese individuals 8. Increased after chidlbirth Quantitative Platelet Disorders Thrombocytopenia Clinical symptoms are usually not seen unless the count falls below 50x10^9/L. Levels below 30x10^9/L results in petechiae, spontaneous bruising, menorrhagia, postoperative or post-traumatic bleeding are observed. When platelet count is below 10 x 10^9/L, the possibility of severe and spontaneous bleeding is high Thrombocytopenia A. Decreased Production 1. Congenital Inherited Thrombocytopenia with small platelets a. Wiskott-Aldrich syndrome (WAS) Also shows decreased platelet aggregation to ADP, epinephrine and collagen; and decreased Tcell number and function b. X-linked thrombocytopenia c. Autosomal dominant with microthrombocytes Thrombocytopenia A. Decreased Production 1. Congenital Inherited Thrombocytopenia with normal size platelets d. Fanconi's anemia/syndrome e. Thrombocytopenia with absent radii (TAR) f. Amegakaryocytic thrombocytopenia - mutation in MPL gene (encoding TPO receptor) g. Familial platelet disorder with a propensity to develop AML h. Quebec platelet disorder i. Dysmegakaryopoietic thrombocytopenia Thrombocytopenia A. Decreased Production 1. Congenital Inherited Thrombocytopenia with Large/Giant platelets a. Bernard - Soulier syndrome Rare inherited blood clotting disorder, large or giant platelets, thrombocytopenia and prolonged bleeding time. b. Mediterranean stomatocytosis/ Macrothrobocytopenia Rare autosomal recessive disorder, enhanced GI absorption, reduced excretion of plant sterols (sitosterolaemia). c. Grey platelet syndrome Macro-thrombocytopenia, absence of platelet -granules resulting in typical gray platelets. Associated with bleeding tendency, myelo brosis and splenomegaly. fi 𝛼 Thrombocytopenia A. Decreased Production 1. Congenital Inherited Thrombocytopenia with Large/Giant platelets d. White platelet syndrome e. May-Hegglin anomaly f. Digeorge's syndrome Thrombocytopenia A. Decreased Production 1. Congenital Inherited Thrombocytopenia with Large/Giant platelets g. Fechtner syndrome h. Epstein syndrome i. Sebastian syndrome j. Paris-Trousseau Thrombocytopenia (Jacobsen's syndrome) k. Down's syndrome l. Homozygous Pelger-Huet anomaly Thrombocytopenia A. Decreased Production 1. Congenital Inherited Thrombocytopenia with Large/Giant platelets m. Giant platelets with mitral valve insu ciency n. Giant platelets with ine ective erythropoiesis o. Montreal platelet syndrome p. Platelet type von Willebrand's disease q. Thrombocytopenia with Neutropenia ff ffi  Thrombocytopenia A. Decreased Production 2. Infection 4. Drugs 5. Ine ective Thrombopoiesis CMV Chemotherapeutic agents: Megaloblastic anemia methotrexate, busulfan, Toxoplasma cytosine arabinoside, 6. Myelophthisis cyclophosphamide, cisplatin. Rubella In ltration of the bone Zidovudine marrow by malignant HIV cells Chlorothiazide diuretics and 3. Radiation tolbutamide Laboratory ndings: Bleeding time: increased when platelet count is less than 100x10^9/L Clot retraction: abnormal if platelet count is 1000 x 10^9/L Surgery Chronic in ammatory disease fl Qualitative Platelet Disorders Qualitative Platelet Disorders I. Inherited Defects A. Adhesion Defects 1. Bernard-Soulier Syndrome (giant platelet syndrome) autosomal recessive lack of membrane receptor Gpib/IX/V presence of giant platelets severe bleeding in homozygotes Laboratory Findings BT: prolonged PT: abnormal; Clot retraction: normal Normal Aggregation with: ADP, epinephrine, collagen, arachidonic acid Does not respond to Ristocetin agglutination Qualitative Platelet Disorders I. Inherited Defects A. Adhesion Defects 2. Von Willebrand’s Disease Characterized by a decrease in production of vWF or production of a dysfunctional protein Qualitative Platelet Disorders I. Inherited Defects B. Aggregation Defects 1. Glanzmann's Thrombasthenia Autosomal recessive lack of gp IIb-Illa serious bleeding problems in homozygotes Qualitative Platelet Disorders I. Inherited Defects B. Aggregation Defects 1. Glanzmann's Thrombasthenia Types of Glanzmann's Thrombasthenia 1. Type 1- undetectable or trace amounts (