Hematology 2 (Finals) Lecture PDF

Hematology 2 (Lecture) Our Lady of Fatima University – Pampanga College of Medical Laboratory Science FINAL TERM LESSON 10: BLEEDING & VASCULAR DISORDERS 4. Epistaxis BLEEDING DISOR...

Hematology 2 (Lecture) Our Lady of Fatima University – Pampanga College of Medical Laboratory Science FINAL TERM LESSON 10: BLEEDING & VASCULAR DISORDERS 4. Epistaxis BLEEDING DISORDERS - Nosebleed Bleeding and vascular disorders are seen on the primary - If bleeding is more than 10 mins, it is considered hemostasis. as hemorrhage. 5. Hemarthrosis HEMORRHAGE - leakage of blood into joint cavities, type of Severe bleeding that requires physical intervention anatomic hemorrhage Medical term for bleeding disorders. 6. Hematemesis Most of the time performed in vivo. - vomiting of blood, common in TB cases Everyone can bleed but not everyone is exposed to 7. Hematoma hemorrhage. - swelling or tumor in the tissues or a body cavity LOCALIZED BLEEDING that contains clotted blood Bleeding from a single location commonly indicates 8. Hematuria injury, infection, tumor, or a blood vessel defect - red cells in urine, no hemolysis (manageable) 9. Hemoglobinuria Blood vessel defect, qualitative platelet defect, reduced - hemoglobin in urine, with hemolysis platelet count, coagulation factor deficiency 10. Melena GENERALIZED BLEEDING - stool containing dark red or black blood Bleeding from multiple sites, spontaneous and 11. Menorrhagia recurring bleeds, or a hemorrhage that requires physical - excessive menstrual bleeding intervention and transfusions (severe blood loss) 12. Hemoptysis Potential evidence for a disorder of primary hemostasis - blood in the sputum, common in TB cases. such as blood vessel defects, platelet defects, Shows evidence of scarring in the lung tissues. thrombocytopenia, secondary hemostasis characterized VASCULAR DISORDERS by single or multiple coagulation factor deficiencies CONNECTIVE TISSUE DISORDERS CLASSIFICATION OF GENERALIZED BLEEDING Found in all (3) blood vessel layers. Generalized bleeding may exhibit a mucocutaneous or a ○ Tunica intima soft tissue pattern ○ Tunica media MUCOCUTANEOUS/SYSTEMIC HEMORRHAGE ○ Tunica externa May appear as petechiae, purpura, ecchymosis, epistaxis, HEREDITARY bleeding gums, hematemesis, menorrhagia; associated EHLERS-DANLOS SYNDROME with disorders of primary hemostasis Associated with hyper extendable joints, hyperelastic skin, ANATOMIC/SOFT TISSUE HEMORRHAGE fragile tissues, bleeding tendency Seen in acquired or congenital defects in secondary Deficiency in the enzyme peptidase, lack of collagen hemostasis, coagulation factor deficiencies MARFAN SYNDROME Includes recurrent or excessive bleeding after minor Associated with long fingers and extremities (legs, trauma, dental extraction, or a surgical procedure arms, fingers) Episodes may even be spontaneous, most anatomic Mutations in the FBN1 gene that codes fibrillin (protein) bleeds are internal, such as bleeds into joints, body Long but not elastic. cavities, muscles, or the central nervous system, and may PSEUDOXANTHOMA ELASTICUM initially have few visible signs Associated with structurally abnormal and calcified C.T BLEEDING DISORDERS elastic fibers, common, wrinkled skin (kulubot) 1. Petechiae (1cm) early as the 3rd trimester - a purpura in which blood escapes into large ACQUIRED areas of skin and mucous membranes only VITAMIN C DEFICIENCY OR SCURVY Vitamin C: most important component for vascular integrity (with collagen) 1  Prevents hydroxylation of the amino acids proline and Increased risk for heavy metal poisoning lysine causing problem in the formation of collagen ENDOTHELIAL DAMAGE Bleeding gums, hemorrhage of subcutaneous tissue, INFECTIOUS PURPURA petechiae on the thighs and buttocks, perifollicular Bacterial: tuberculosis (strep pyogenes), scarlet petechiae fever(strep pyogenes), typhoid fever (salmonella typhi), SENILE PURPURA diphtheria, endocarditis, Waterhouse-Friedrichsen Common among elders syndrome Associated with degeneration of collagen, elastin, and Waterhouse-Friedrichsen syndrome: subcutaneous fat ○ Caused by Neisseria meningitis (causes CORTICOSTEROID PURPURA purpura fulminans) Can be due to aging ○ Excessive lysis and formation Cushing’s disease/Hypercortisolism: (pathologic cause) ○ DIC: cause of death is usually toxic shock and ○ Increased glucocorticoids, especially cortisol, overload which is a steroid hormone, which causes Viral: smallpox, influenza, measles abnormal enlargement of muscle/vessel, Rickettsial: RMSF (Rocky Mountain Spotted Fever) increased testosterone caused by Rickettsia rickettsi Cortisol - regulates inflammation and Protozoal: Malaria caused by Plasmodium spp. (stays in blood sugar. Stress hormones. the RBC) ○ Signs and symptoms: moon face, buffalo hump, AUTOIMMUNE VASCULAR PURPURA pink or purple stretch marks Allergic purpuras/Anaphylactoid SCHAMBERG’S PURPURA ○ Also known as Henoch-Schonlein purpura (if Progressive pigmented purpura, leakage on the tissues there’s bleeding in both the GI and joints) and red cells are hemolyzed ○ Associated with: Petechiae: Cayenne pepper purpura appearance Abdominal pain secondary to (orange) gastrointestinal hemorrhage (henoch Various skins problems leading to purpura; red cells can purpura) easily escape out Joint pain in the knees, ankles, wrists (schonlein purpura) ALTERED VESSEL WALL STRUCTURE DRUG INDUCED PURPURA HEREDITARY quinine, procaine, penicillin, aspirin, sulfonamides, HEREDITARY HEMORRHAGIC TELANGIECTASIA (HHT) sedatives, warfarin, barbiturates, diuretics, digoxin, Telangiectasia: vascular malformations and surface skin methyldopa lesions MISCELLANEOUS ABNORMALITIES CAUSING PURPURA BV are disorganized and dilated throughout the body with SECONDARY TO VESSEL DAMAGE: decreased ability to contract ACQUIRED Lesions develop on the tongue, lips, palate, face, and Waldenstrom Macroglobulinemia hands Kaposi’s sarcoma Common symptom is Iron deficiency anemia Hemochromatosis Also known as Osler Weber Rendu disease Snake venom CONGENITAL PURPURA OF UNKNOWN ORIGIN HEMANGIOMATA/HEMANGIOMA-THROMBOCYTOPENIA PURPURA SIMPLEX SYNDROME Simple purpura, Devil’s pinches, simple vascular or Associated with abnormal tumors in which blood vessels vascular fragility occurs because of skin fragility bleed at the surface PSYCHOGENIC PURPURA Tumors can lead to formation of fibrin clots, platelet Seen in individuals with emotional problems, often after consumption, red cell destruction secondary to vascular severe trauma or extensive surgery, which may be obstruction hypersensitive to RBC membrane components or DNA Platelet trapping demonstrated by immunohistochemical hypersensitivity staining of the tumors with anti-CD61 antibodies Associated with thrombocytopenia Also known as Kasabach Merritt Syndrome ACQUIRED DIABETES MELLITUS (TYPE 2) BV may become atherosclerotic (sugar deposits), and thickening of the basement membrane of the capillaries Can damage the renal glomeruli and cause retinal blindness AMYLOIDOSIS Associated with vessel obstruction due to deposition of amyloid ○ Amyloid should be part of the excretion process. HEMATOLOGY 2 MAKATAK 2  LESSON 11: PLATELET DISORDERS INFILTRATION OF THE BONE MARROW BY MALIGNANT GENERAL OVERVIEW CELLS Bleeding disorders are observed in two (2) means: Thrombocytopenia associated with abnormal cells ○ Superficial - seen easily as a symptom crowding or replacing normal cells Due to platelets or problem with blood Associated with metastatic tumor, myelofibrosis, leukemia vessel walls ○ Deep tissue - due to coagulation factors ADDITIONAL INFOS: Quantitative: pathophysiologic process that result in Production involves the maturation series of blood groups thrombocytopenia and thrombocytosis or stem cells involving the megakaryocytes. ○ Thrombocytopenia - below the normal platelet Congenital Hypoplasia of Megakaryocytes count, 450,000 /uL ○ Either low production or differentiation does not Qualitative: defects in platelet function happen. ○ Correlates with congenital problems INEFFECTIVE THROMBOPOIESIS QUANTITATIVE PLATELET DISORDERS ACQUIRED THROMBOCYTOPENIA Characterized by normal to increased marrow megakaryocytes but decreased circulating platelets IMPAIRED OR DECREASED PRODUCTION ○ Sign called compensation. CONGENITAL HYPOPLASIA OF MEGAKARYOCYTES Alcohol-related thrombocytopenia: secondary to FANCONI’S ANEMIA ethanol interruption of megakaryocyte differentiation Congenital form of aplastic anemia Megaloblastic states: secondary to impaired DNA ○ Aplastic - absence/lack of cells due to a bone synthesis due to Vit. B12 and B9 deficiency marrow failure ○ DNA impaired = glossy megakaryocytes THROMBOCYTOPENIA ABSENT RADIUS (TAR) SYNDROME appearance in the BM with a deformed dumbbell Associated with a mutation in the RBM8A gene resulting shaped nuclei to absence or decreased BM megakaryocytes; a rare Severe IDA: Iron is essential for enzyme systems involved disease first identified in 1959 in platelet protein synthesis Platelet count: 10,000 - 30,000 /uL (2 years of infancy Paroxysmal nocturnal hemoglobinuria: platelets have observable) abnormal sensitivity to complement and antibodies Congenital deformities in the arm or bone in the arm HEREDITARY Managed by platelet transfusion MYH9 RELATED THROMBOCYTOPENIA SYNDROMES CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA Caused by mutations in the MYH9 gene; affected patients (CAMT) have a triad of thrombocytopenia, macrothrombocytes, Mutation in the MPL gene that results to the loss of TPO and May-Hegglin granules (associated with mRNA receptor problems) Presence of severe thrombocytopenia, absence of Giant platelets = low platelet count megakaryocytes in the bone marrow Examples: May-Hegglin anomaly, Sebastian syndrome, Focused in the BM failure but the megakaryocytes are the Epstein syndrome, Fechtner syndrome only ones affected WISKOTT ALDRICH SYNDROME Decreased megakaryocytes and platelet count Associated with microthrombocytopenia SELECTIVE SUPPRESSION OF MEGAKARYOCYTES Defect in the release or production of platelets granules or Chlorothiazide deficiency in dense granules ○ Type of sulfonamides that have a cytotoxic effect INCREASED PLATELET DESTRUCTION in the fetal marrow. IMMUNOLOGIC CAUSE VIRAL INFECTIONS: Associated with immunologic disorders leading to Rubella increased platelet destruction Cytomegalovirus (CMV) Increased levels of immunoglobulins/antibodies, ○ Most common infectious agent causing complement on the platelet surface, Antigenic congenital thrombocytopenia determinants associated with immune platelet destruction: ACQUIRED HYPOPLASIA OF MEGAKARYOCYTES: HLA, ABO, Platelet alloantigens Due to exposure to: ISOIMMUNE CAUSE (ISOANTIBODY / ALLOANTIBODY) ○ Drugs (drug induced hypoplasia) Post- transfusion purpura (PTP) ○ Chemicals ○ Alloantibodies against platelet specific antigen ○ Chemotherapy (due to the excessive (P1A1) medications) ○ Platelet count: 10 fold in homozygous Proportional decrease in the level and activity of protein S cystathionine-ß-synthase TYPE II > quali - Congenital: low levels of an enzymes necessary for the Normal levels of free and bound protein S, abnormal conversion of homocysteine to cysteine which increase function due to genetic alteration in the genetic sequence the risk of a clotting event TYPE III > quanti - FACTOR V LEIDEN MUTATION Normal level of total protein S but with a clinically · ↳ free a bound In 1993, a new and very common inherited thrombophilic significant decrease in free protein S Levels thrombosis PROTEIN C DEFICIENCY syndrome was described; APC Mutation happens in the Factor V protein which is known Leads to recurrent superficial or deep vein thrombosis incombin - as the “Leiden protein” (DVT) and frequent pulmonary emboli Thrombomodulin complex Molecular defect (single point mutation) was identified TYPES: ↳ protein involving the transition of guanine (G) to adenine (A) at TYPE I: & (w/ nucleotide 1691 of the Factor V gene Low protein C levels and activity protein S Mutation results in the substitution of arginine (R) with TYPE II: inactivates FV and glutamine (Glu) at number 506 : Low protein C activity due to genetic of protein C x VIII Homozygous: sequence resulting to abnormal function Possess only the Leiden Protein and an 80-fold HOMOZYGOUS PROTEIN C DEFICIENCY increased risk of clotting disorder compared to the general Appears in newborn infants; cause Purpura fulminans in unaffected population children Heterozygous: WARFARIN INDUCED SKIN NECROSIS Produce about 50% of Leiden Protein and have 5-7 fold Cause a rapid drop in Protein C and Factor VII resulting in increased risk of clotting disorder compared to the general super clotting state in the extremities population LUPUS ANTICOAGULANT DEFICIENCY Other Factor V mutation: Inhibits the action of prostacyclin and platelet Factor V Cambridge mutation Kalabak 1 phospholipids Factor V Hong Kong mutation -- TXa2 Prostacyclin: inhibits platelet aggregation ELEVATED LEVELS OF CLOTTING FACTORS Excessive platelet aggregation results in excessive clot Elevated levels of other procoagulants can also be formation HEMATOLOGY 2 MAKATAK 14  HEPARIN CO-FACTOR II (HC-II) DEFICIENCY glutamic acid by slowing the activity of the enzyme vitamin Deficiency leads to increased thrombi formation due to K epoxide reductase low/deficient activity to inhibit thrombin ↑ slut formation Activities of factors II, VII, IX, and X and proteins C, S, and TYPES: Z become reduced as the nonfunctional des-carboxyl TYPE I: > quali 3 quanti - proteins are produced in their place (PIVKA) Prevent post-VTE rethrombosis, ischemic stroke Decreased in both levels and functional capacity Monitored by: PT (based on the INR results) TYPE II: > quali - Administration: oral Decreased in the functional capacity but with normal levels Overdose treated by oral or intravenous Vitamin K; if of heparin co-factor II bleeding occurs: FFP, recombinant factor VII, prothrombin THROMBOMODULIN DEFICIENCY complex concentrate Small thrombomodulin fragments circulates in soluble form DIRECT THROMBIN INHIBITORS (DTI) in plasma of health individuals Argatroban and bivalirudin are intravenous Binds to thrombin inhibiting the action of thrombin anticoagulants that are substituted for UFH in patients who Deficiency is seen in patients with venous and arterial have developed heparin-induced thrombocytopenia with clotting conditions and DIC thrombosis (HIT), a devastating arterial and venous fibrinolytic ( PLASMINOGEN DEFICIENCY thrombotic side effect of UFH therapy Deficiency primarily involves the veins causing Dabigatran: an oral DTI cleared in 2010 to prevent thrombophlebitis and stroke ischemic stroke, a common side effect for patients who There is a deficiency in the plasminogen that can cause suffer non-valvular atrial fibrillation clot lysis * clot ANTI-PLATELET FUNCTION THERAPY TYPES: Used to treat arterial thrombosis; Prevent acute TYPE I: quali and quanf coronary syndrome recurrence Proportional decrease on the level of fibrinogen and its ASPIRIN: activity Irreversibly acetylates the platelet enzyme TYPE II: quali cyclooxygenase at the serine in position 529 Also called as dyplasminogenemia; decrease function of Prevents production of Thromboxane A2 (responsible for plasminogen aggregation) ANTITHROMBOTIC THERAPY CLOPIDOGREL, PRASURGEL, TICAGRELOR GENERAL OVERVIEW & Members of the thienopyridine drug family Pampanipis Include anticoagulants, which suppress coagulation and ud Occupy the platelet membrane adenosine diphosphate reduce thrombin formation, and antiplatelet drugs, which dugo (ADP) receptor P2Y12 suppress platelet activation (blood Suppressing the normal platelet aggregation and secretion thinners Fibrinolytics are also employed to disperse or reduce response to the activating ligand (agonist) ADP existing clots clogging veins and arteries OTHERS: ANTICOAGULANT THERAPY NSAID’s: Phenylbutazone and Indomethacin UNFRACTIONATED HEPARIN (UFH) THERAPY Antibiotics: Penicillin and Cephalosporin Anti-depressants: Chlorpromazine Used to prevent thrombi formation in veins Propanolol, Beta-blockers, Diuretics, Sulfinpyrazone, Heparin: inactivates the serine proteases factors IIa, IXa, Dextran and alcohol Xa, XIa, XIIa Venous thromboembolic enents/discuse Administer intravenously to treat VTE, to provide initial treatment of AMI, to prevent reocclusion after stent placement, and to maintain vascular patency during cardiac surgery using cardiopulmonary bypass (CPB) with extracorporeal circulation Half-life: 1-2 hours Types: ○ Low Molecular Weight Heparin (LMWH) ○ High Molecular Weight Heparin (HMWH) Administration: IV infusion, subcutaneous injection Monitored by: aPTT Protamine sulfate/Histamine: to prevent excessive bleeding due to heparin ORAL ANTICOAGULANT THERAPY Coumarin/Coumadin (brand name: warfarin) and Dicoumarol Coumarin: also known as 4-hydroxycoumarin, warfarin sodium vitamin K antagonist that suppresses g-carboxylation of HEMATOLOGY 2 MAKATAK 15