Extrinsic Hemolytic Anemias Lecture Notes PDF

MLS 3102: HEMATOLOGY I LECTURE EXTRINSIC HEMOLYTIC ANEMIAS Mrs. Cherry Grace A. Dabucon, MD 1st Semester A.Y. 2024-2025 OUTLINE A.​ THROMBOTIC THROMBOCYTOPENIC PURPURA...

MLS 3102: HEMATOLOGY I LECTURE EXTRINSIC HEMOLYTIC ANEMIAS Mrs. Cherry Grace A. Dabucon, MD 1st Semester A.Y. 2024-2025 OUTLINE A.​ THROMBOTIC THROMBOCYTOPENIC PURPURA I.​ Plasma Constituent V.​ Miscellaneous ​ (NON-IMMUNOLOGIC): MAHA Abnormalities Extracorpuscular ​ Etiology II.​ Extrinsic Hemolytic Mechanism of Injury 1.​ Idiopathic – autoantibodies to ADAMTS-13 Anemias VI.​ Immune Hemolytic 2.​ Secondary – infections, pregnancy, inflammation, III.​ Microangiopathic Anemias and disseminated malignancy depressing Hemolytic Anemias VII.​ Autoimmune ADAMTS-13 synthesis (MAHAs) Hemolytic Anemia 3.​ Inherited – also Upshaw-Schülman syndrome a.​ Thrombotic VIII.​ Drug-Induced Immune ​ Aka Moschcowitz syndrome, is characterized by the triad thrombocytope Hemolytic Anemia of: nic purpura IX.​ Alloimmune Hemolytic 1.​ microangiopathic hemolytic anemia (MAHA) b.​ Hemolytic Anemia 2.​ Thrombocytopenia Uremic X.​ Anemia of Blood Loss 3.​ neurologic abnormalities Syndrome XI.​ DAT & IAT ​ Deficiency in ADAMTS 13 [(a disintegrin and metalloprotease (HUS) with a thrombospondin type 1 motif, member 13)] enzyme or c.​ HELLP block its function. (a vWF-cleaving protease) Syndrome ➔​ (a vWF-cleaving protease) - primarily synthesized d.​ Disseminated in the liver, and its major function is to cleave von Intravascular Willebrand factor anchored on the endothelial Coagulation surface in circulation, and at the sites of vascular (DIC) injury. IV.​ Macroangiopathic ➔​ Formation of hyaline thrombi (platelets + VWF) in Hemolytic Anemia capillaries and arterioles throughout the body ​ Treatment: Most effective is plasma exchange using FFP or cryoprecipitate poor plasma. ➔​ Cryoprecipitate-poor Plasma Contains all I.​ PLASMA CONSTITUENT ABNORMALITIES coagulation factors except von Willebrand's 1.​ Abetalipoproteinemia factor and factor VIII. 2.​ LCAT Deficiency ○​ Lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare (AR) genetic disorder that affects the body's ability to process cholesterol. ○​ LCAT is an enzyme in the plasma that's mainly produced in the liver. It's responsible for forming mature HDL cholesterol and moving cholesterol from peripheral tissues to the liver. ○​ LCAT deficiency comes in two forms: 1.​ Familial LCAT deficiency: A complete deficiency of LCAT 2.​ Fish-eye disease: A partial deficiency of LCAT ​ Manifestations: a.​ Corneal opacities: A clouding of the front surface of the eye. b.​ Hemolytic anemia: A shortage of red blood cells caused by the breakdown of red blood cells c.​ Kidney failure: Excess cholesterol is deposited in the kidneys, damaging the cells ➔ proteinuria d.​ Hyperlipidemia ​ Laboratory Findings in TTP 1.​ Hb typically below 10 g/dL 2.​ Severe thrombocytopenia (10-30 X 109/L) 3.​ PBS: reticulocytosis, nRBCS, large # of schistocytes (hallmark), poikilocytosis 4.​ Coagulation tests: within reference range 5.​ Chemistry: increased plasma LDH, Hb and B1; decreased haptoglobin II.​ EXTRINSIC HEMOLYTIC ANEMIAS ​ RBCs are structurally & functionally normal, but a condition outside causes premature hemolysis. ​ Causes: 1.​ Nonimmune – presence of a condition that causes physical/mechanical injury to RBCs B.​ HEMOLYTIC UREMIC SYNDROME 2.​ Immune – mediated by antibodies, complement, or ​ Occurs in children after gastrointestinal infection with both Shigella dysenteriae serotypes and E. coli serotype O157:H7 ​ NONIMMUNE HEMOLYTIC ANEMIA ​ Toxins enter bloodstream and attach to renal glomerular cells 1.​ Microangiopathic hemolytic anemia Two general types. ➔​ Thrombotic thrombocytopenic purpura ○​ Shigella dysenteriae serotypes - ➔​ Hemolytic uremic syndrome (Abdominalpain,Bloody diarrhea,Vomiting.) ➔​ HELLP syndrome ​ Cardinal signs: hemolytic anemia, renal failure, and ➔​ Disseminated intravascular coagulation thrombocytopenia 2.​ Macroangiopathic hemolytic anemia ○​ Intravascular clotting is confined in the kidney ➔​ Traumatic cardiac hemolytic anemia *Lack of neurologic symptoms ➔​ Exercise-induced hemoglobinuria 3.​ Infection -​ Malaria, Babesiosis, Clostridial sepsis, Bartonellosis 4.​ RBC Injury due to other causes ➔​ Chemicals, drugs, venoms, extensive burns III.​ MICROANGIOPATHIC HEMOLYTIC ANEMIAS ​ Microangiopathic: a disease of small vessels. ​ Can be caused by a complication of one of several conditions ​ Laboratory Findings in HUS in which there is a disturbance of the microvascular 1.​ PBS: severely decreased Hb (4 environment. g/dL), leukocytosis, 1.​ Thrombotic thrombocytopenic purpura (TTP) thrombocytopenia, schistocytes, 2.​ Hemolytic uremic syndrome (HUS) burr cells 3.​ HELLP (hemolysis, elevated liver enzymes, low 2.​ Coagulation tests: within platelet count) syndrome reference range 4.​ Disseminated intravascular coagulation (DIC) Tumalaytay 1  3.​ Chemistry: markedly elevated plasma Hb, ○​ Malaria is the most common decreased haptoglobin infectious disease that 4.​ Urinalysis: albuminuria, RBCs, WBCs, casts causes a HA ○​ Extracellular infections: T. C.​ HELLP SYNDROME gondii, Clostridium ​ (Hemolysis, Elevated Liver enzymes, and Low Platelet count) perfringens, Staphylococcus, ​ benign physiologic condition that is the most common cause of Streptococcus thrombocytopenia in pregnancy and requires no evaluation or treatment 2.​ Exposure to chemicals and toxins ​ Preeclampsia (a serious blood pressure condition that ○​ Spiders and snakes (rarely) develops during pregnancy) and other hypertensive disorders venom contain enzymes that lyze the RBC of pregnancy. membrane ​ Mechanism of platelet destruction is unclear -After delivery, ○​ Hemotoxins cause hemolysis, or induce blood the thrombocytopenia usually resolves in a few days coagulation (clotting) ​ Some patients with preeclampsia have microangiopathy 3.​ Thermal Injury -​ Microangiopathy - the capillary walls become so ○​ Heat (third degree burns) cause direct damage to thick and weak that they bleed, leak protein, and RBC membrane causing RBCs to fragment slow the flow of blood. ​ Major diagnostic criteria: low APC, increased LDH and AST VI.​ IMMUNE HEMOLYTIC ANEMIAS ​ Treatment: The best treatment of preeclampsia is delivery of ​ RBC survival is shortened due to an the infant whenever possible antibody-mediated mechanism ➔​ Autoantibody ➔​ Alloantibody ➔​ Drug antibody ​ Associated with a positive DAT ​ Pathophysiology of Immune Hemolysis a.​ IgM ➔​ Requires complement ➔​ Hemolysis may be extravascular D.​ DISSEMINATED INTRAVASCULAR COAGULATION (mainly in the liver) if ​ Widespread activation of the hemostatic system resulting complement is to fibrin- thrombi formation in small vessels. partially activated to ​ Multiple organ failure can occur due to clotting and bleeding C3b, or intravascular due to consumption of platelets. if complement is fully ​ Basic Causes of DIC activated to C9. 1.​ Release of tissue thromboplastin-like substances b.​ IgG Obstetric complications, burns, etc ➔​ Occurs with or without complement 2.​ Activation of coagulation proteins by damaged activation endothelium infections (viral, bacterial, fungal), heat ➔​ IgG-sensitized RBCs are removed from stroke, shock the circulation by macrophages in the 3.​ Activation of coagulation proteins in association spleen with intravascular aggregation of platelets Toxins and drugs. VII.​ AUTOIMMUNE HEMOLYTIC ANEMIA ​ Clinical Manifestations: ​ AIHA is caused by an altered immune response resulting in 1.​ Ischemia of major organ microvasculature ➔organ production of antibodies against the hosts own RBC dysfunction such as renal function impairment, ​ Classification: acute respiratory distress syndrome, 2.​ Central nervous system manifestations such as 1.​ Warm AIHA – 70% of cases of AIHA sudden vision loss or seizures. ○​ Majority are caused by IgG (rarely IgM, IgA) 3.​ Skin, bone, and bone marrow necrosis may be antibodies. seen. Purpura and ecchymoses are seen in ○​ Antibodies bind optimally @ 37°C meningococcemia, chickenpox, and spirochete ○​ Hemolysis usually extravascular (Ag-Ab complexes infections are cleared by the spleen) ​ Treatment of DIC ○​ Classification/Etiology: 1.​ Treat the underlying cause a.​ Idiopathic – 60% of cases 2.​ Fluid therapy b.​ Secondary to diseases that alter the 3.​ UFH (unfractionated Heparin) –antithrombotic immune response (lymphoproliferative 4.​ FFP, PC, PRBC diseases, autoimmune disorders, immunodeficiency disorders, viral infections) ○​ Anemia is mild to severe ○​ Laboratory: spherocytes; ↑ OFT; positive (DAT helpful in differentiating from hereditary spherocytosis) 2.​ Cold Agglutinin Disease (CAD)– 15-20% of AIHA ​ Laboratory Diagnosis of DIC =requires speedy laboratory ○​ Caused by IgM with optimum confirmation DIC Profile: reactivity at 4°C and a thermal 1.​ a platelet count → thrombocytopenia amplitude >30°C 2.​ blood film examination → schistocytes (MAHA) ○​ Ab binds to RBCs at cold temp + 3.​ PT, PTT → prolonged Complement, at central 4.​ Thrombin Time - prolonged (warmer) circulation IgM 5.​ fibrinogen assay -