Cambridge Hematology Short Notes PDF

CAMBRIDGE Hematology SHORT NOTES Essential Guide for Doctors & Medical Students 1ST EDITION Title: Cambridge Hematology Short Notes : Essential Guide for Doctors and Medical Students Edition : First Edition Author: Dr. Rish T Publisher:...

CAMBRIDGE Hematology SHORT NOTES Essential Guide for Doctors & Medical Students 1ST EDITION Title: Cambridge Hematology Short Notes : Essential Guide for Doctors and Medical Students Edition : First Edition Author: Dr. Rish T Publisher: Cambridge Medical Books Copyright © 2024 Dr. Rish T All rights reserved. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means without the prior written permission of the publisher. Disclaimer The information provided in this book is for academic purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Acknowledgments I would like to express my deepest gratitude to my colleagues and mentors who provided invaluable insights and support throughout the writing process. Special thanks to Dr. Mash for her thorough review and constructive feedback. I also extend my heartfelt thanks to my family for their patience and understanding.  Chapters 1. Red Blood Cell Disorders Lymphomas Anemias o Hodgkin's Lymphoma o Iron Deficiency Anemia o Non-Hodgkin's Lymphoma o Vitamin B12 Deficiency Anemia (Pernicious Anemia) Plasma Cell Disorders o Folate Deficiency Anemia o Multiple Myeloma o Hemolytic Anemia o Waldenström's Macroglobulinemia o Sickle Cell Anemia o Monoclonal Gammopathy of o Thalassemias (Alpha and Beta) Undetermined Significance (MGUS) o Aplastic Anemia Other WBC Disorders o Anemia of Chronic Disease o Neutropenia Hemoglobinopathies o Lymphocytosis o Sickle Cell Disease o Eosinophilia o Thalassemias o Myelodysplastic Syndromes (MDS) o Hemoglobin C Disease o Chronic Granulomatous Disease o Hemoglobin E Disease 3. Platelet Disorders Other RBC Disorders Thrombocytopenia o Polycythemia Vera o Immune Thrombocytopenic Purpura o Hereditary Spherocytosis (ITP) o G6PD Deficiency o Thrombotic Thrombocytopenic o Paroxysmal Nocturnal Purpura (TTP) Hemoglobinuria (PNH) o Heparin-Induced Thrombocytopenia (HIT) 2. White Blood Cell Disorders o Disseminated Intravascular Leukemias Coagulation (DIC) o Acute Lymphoblastic Leukemia Thrombocytosis (ALL) o Essential Thrombocythemia o Acute Myeloid Leukemia (AML) Qualitative Platelet Disorders o Chronic Lymphocytic Leukemia (CLL) o Bernard-Soulier Syndrome o Chronic Myeloid Leukemia (CML) o Glanzmann's Thrombasthenia 4. Coagulation Disorders 6. Hematologic Malignancies Hemophilia Leukemias o Hemophilia A (Factor VIII Lymphomas Deficiency) Multiple Myeloma o Hemophilia B (Factor IX Myelodysplastic Syndromes Deficiency) Myeloproliferative Neoplasms Von Willebrand Disease o Type 1 7. Transfusion Medicine o Type 2 (A, B, M, N) Transfusion Reactions o Type 3 o Hemolytic Transfusion Reactions Acquired Coagulation Disorders o Febrile Non-Hemolytic o Liver Disease Transfusion Reactions o Vitamin K Deficiency o Allergic Reactions o Anticoagulant Therapy (Warfarin, o Transfusion-Related Acute Lung Heparin) Injury (TRALI) Thrombophilia o Transfusion-Associated o Factor V Leiden Circulatory Overload (TACO) o Prothrombin Gene Mutation Blood Component Therapy o Antithrombin Deficiency o Red Blood Cell Transfusion o Protein C and S Deficiency o Platelet Transfusion o Antiphospholipid Syndrome o Plasma Transfusion o Cryoprecipitate Transfusion 5. Bone Marrow Disorders Aplastic Anemia 8. Hemoglobin Disorders Myeloproliferative Disorders Thalassemias o Polycythemia Vera Sickle Cell Disease o Essential Thrombocythemia Hemoglobin C Disease o Myelofibrosis Hemoglobin E Disease o Chronic Myeloid Leukemia (CML) Myelodysplastic Syndromes (MDS) Paroxysmal Nocturnal Hemoglobinuria (PNH)  Red Blood Cell 1 Disorders Anemias o Iron Deficiency Anemia o Vitamin B12 Deficiency Anemia (Pernicious Anemia) o Folate Deficiency Anemia o Hemolytic Anemia o Sickle Cell Anemia o Alpha Thalassemias o Beta Thalassemias o Aplastic Anemia o Anemia of Chronic Disease Hemoglobinopathies o Sickle Cell Disease o Hemoglobin C Disease o Hemoglobin E Disease Other RBC Disorders o Polycythemia Vera o Hereditary Spherocytosis o G6PD Deficiency o Paroxysmal Nocturnal Hemoglobinuria (PNH)  Iron Deficiency Anemia Definition Clinical Features Iron Deficiency Anemia (IDA) is a General symptoms: Fatigue, pallor, microcytic, hypochromic anemia caused weakness, dyspnea on exertion by insufficient iron, leading to inadequate Specific symptoms: Pica (craving for hemoglobin synthesis. non-food substances), angular stomatitis, koilonychia (spoon-shaped Etiology nails) Dietary deficiency: Inadequate intake In severe cases: Tachycardia, glossitis of iron-rich foods (e.g., vegetarian diets) Increased demand: Pregnancy, Diagnosis lactation, growth spurts in children Blood tests: Chronic blood loss: Gastrointestinal o Hemoglobin: Low bleeding (e.g., peptic ulcer, malignancies), menstrual bleeding o MCV (Mean Corpuscular Volume): Low (microcytic) Malabsorption: Celiac disease, gastric surgery (e.g., gastrectomy, o MCH (Mean Corpuscular bariatric surgery) Hemoglobin): Low (hypochromic) Pathophysiology o Serum ferritin: Low (most Iron is essential for hemoglobin sensitive early indicator) synthesis. Deficiency results in o Serum iron: Low reduced erythropoiesis and smaller, hypochromic red blood cells. o TIBC: Elevated Stages: o Transferrin saturation: Low 1. Depletion of iron stores: Peripheral blood smear: Microcytic, Decreased ferritin, normal RBC hypochromic RBCs indices Bone marrow biopsy: Absent iron 2. Iron-deficient erythropoiesis: stores (rarely indicated) Reduced serum iron, increased total iron-binding capacity (TIBC) 3. Iron deficiency anemia: Microcytic, hypochromic RBCs, reduced hemoglobin Differential Diagnosis Monitoring Anemia of chronic disease Reticulocyte count increases in Thalassemia 1-2 weeks after starting treatment. Sideroblastic anemia Hemoglobin normalization in 6- 8 weeks; continue iron therapy Management for 3-6 months to replenish stores. Identify and treat the underlying cause: o Control bleeding, address Complications malabsorption, or improve Delayed growth and cognitive diet. development in children Iron supplementation: Pregnancy complications: o Oral iron: Ferrous sulfate (325 Preterm delivery, low birth mg) 1-3 times/day for 3-6 weight months; side effects include Cardiac failure in severe GI upset, constipation. anemia o Intravenous iron: Indicated for malabsorption, intolerance to oral iron, or severe deficiency (e.g., ferric carboxymaltose). Dietary advice: o Increase intake of iron-rich foods (e.g., red meat, beans, fortified cereals) and vitamin C to enhance absorption. Blood transfusion: Reserved for symptomatic severe anemia or cardiac compromise.  Vitamin B12 Deficiency Anemia (Pernicious Anemia) Definition Pernicious Anemia: A type of macrocytic anemia Autoimmune destruction of parietal cells → decreased IF → caused by insufficient absorption impaired absorption of B12 in of Vitamin B12, commonly due to the ileum → megaloblastic autoimmune destruction of anemia. gastric parietal cells (pernicious anemia) or dietary deficiency. Clinical Features Causes General: Fatigue, weakness, pallor. Autoimmune: Pernicious anemia (antibodies against Neurological: Peripheral intrinsic factor or gastric neuropathy, paresthesia, parietal cells). ataxia, cognitive disturbances Dietary: Vegan or vegetarian (due to demyelination of nerves). diets, malnutrition. GI: Glossitis, diarrhea, loss of Gastrointestinal disorders: appetite, weight loss. Atrophic gastritis, Crohn’s disease, celiac disease, Hematologic: Megaloblastic gastrectomy, ileal resection. anemia (macrocytic), thrombocytopenia, Medications: Proton pump inhibitors, metformin. neutropenia. Pathophysiology B12 Absorption: Requires intrinsic factor (IF) produced by gastric parietal cells. Diagnostic Workup Maintenance Therapy: CBC: Macrocytic anemia, Lifelong B12 supplementation low hemoglobin, elevated in pernicious anemia. MCV (>100 fL). Neurological Symptoms: May Peripheral Smear: be irreversible if not treated Hypersegmented early. neutrophils, macrocytes. Serum B12 Levels: Low Complications (10% in 6 months) Exact cause unknown but Pruritus (itching), fatigue associated with Epstein-Barr Virus (EBV) in some cases. Alcohol-induced lymph node pain (rare but characteristic) Risk factors: Family history, immunosuppression (e.g., HIV), history of infectious Diagnosis mononucleosis. Lymph Node Biopsy: Presence of Reed-Sternberg cells (large, Subtypes binucleate cells with “owl-eye” appearance). 1.Classical Hodgkin's Lymphoma (CHL): Immunohistochemistry: CD15+, CD30+ (for classical o Nodular Sclerosis (most common) HL). Staging Investigations: o Mixed Cellularity o PET/CT scan: Assess extent o Lymphocyte-rich of disease. o Lymphocyte-depleted o Bone marrow biopsy: For 2.Nodular Lymphocyte- advanced stages. Predominant Hodgkin's Lymphoma (NLPHL): Less common, non-classical variant. Staging (Ann Arbor Staging) Targeted therapy: Brentuximab Stage I: Involvement of a single vedotin (anti-CD30), PD-1 inhibitors for relapsed/refractory lymph node region. cases. Stage II: Two or more lymph node regions on the same side of the diaphragm. Prognosis Stage III: Lymph nodes on both Excellent overall survival with sides of the diaphragm. treatment, especially in early- stage disease. Stage IV: Disseminated involvement (liver, bone marrow, 5-year survival rate >90% in etc.). early-stage HL, but lower in advanced stages or relapsed cases. Treatment Early-stage (I/II): Follow-up o ABVD chemotherapy Regular monitoring with PET/CT (Adriamycin, Bleomycin, scans. Vinblastine, Dacarbazine). Long-term follow-up for o Involved-site radiation therapy (ISRT). treatment-related complications (e.g., secondary Advanced-stage (III/IV): malignancies, cardiovascular o ABVD or BEACOPP regimen disease). (Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone). o Stem cell transplantation for refractory or relapsed disease. Non-Hodgkin's Lymphoma (NHL) Definition Clinical Features A heterogeneous group of Painless lymphadenopathy (can lymphoid malignancies originating be localized or generalized). from B-cells, T-cells, or NK cells, B symptoms: Fever, night distinct from Hodgkin’s sweats, weight loss (>10%). lymphoma. Extranodal involvement: Gastrointestinal tract, skin, Epidemiology CNS, bone marrow. More common than Hodgkin's Symptoms depend on site of lymphoma. involvement (e.g., abdominal mass, skin lesions, CNS Incidence increases with age. symptoms). Risk factors: Immunosuppression (HIV, transplant patients), Diagnosis autoimmune diseases, Lymph node biopsy: Gold infections (e.g., EBV, HTLV-1, H. standard for diagnosis. pylori), exposure to chemicals (e.g., pesticides). Immunophenotyping: Determines cell type (B or T cell). Classification Staging: Ann Arbor staging B-cell NHL (85% of cases): system (I-IV). e.g., Diffuse large B-cell Imaging: CT, PET-CT for staging lymphoma (DLBCL), Follicular and assessment of extranodal lymphoma, Mantle cell involvement. lymphoma. Bone marrow biopsy: To T-cell NHL (15%): e.g., assess marrow involvement. Peripheral T-cell lymphoma, Anaplastic large cell lymphoma. Prognostic Factors Prognosis International Prognostic Index Varies by subtype, grade, and (IPI): Factors include age, stage. performance status, stage, Indolent lymphomas may have extranodal involvement, and LDH a long natural history but are levels. not curable. Aggressive lymphomas can be Management curable with treatment but are rapidly progressive if untreated. Low-grade (indolent) NHL: Observation in asymptomatic cases, rituximab-based therapy, Complications radiotherapy for localized disease. Indolent lymphomas may have a long natural history but are High-grade (aggressive) NHL: not curable. Chemotherapy (e.g., CHOP - Cyclophosphamide, Aggressive lymphomas can be Doxorubicin, Vincristine, curable with treatment but are Prednisone), often combined rapidly progressive if untreated. with Rituximab (anti-CD20 Bone marrow failure monoclonal antibody). Infections (due to Relapsed/refractory disease: immunosuppression), High-dose chemotherapy CNS involvement followed by autologous stem cell transplant, CAR-T cell Secondary malignancies. therapy for some subtypes. CNS involvement: Intrathecal chemotherapy.  Multiple Myeloma Definition CRAB Symptoms A malignant proliferation of plasma o C: Hypercalcemia (due to bone cells in the bone marrow, leading to resorption) excessive monoclonal immunoglobulin production (usually IgG or IgA). o R: Renal failure (Bence Jones proteinuria) Epidemiology o A: Anemia (bone marrow infiltration) More common in elderly patients (median age ~65-70 years) o B: Bone pain and pathological fractures (lytic bone lesions) Slight male predominance Other symptoms: recurrent infections, Higher incidence in African American fatigue, weight loss populations Diagnosis Pathophysiology Blood tests: Clonal plasma cells produce a large o Monoclonal (M) protein in amount of monoclonal protein (M- serum/urine (SPEP, UPEP) protein). o Hypercalcemia, renal Bone marrow infiltration by malignant dysfunction, anemia plasma cells causes: o Increased serum β2- o Bone destruction (osteolytic microglobulin (prognostic marker) lesions) Bone marrow biopsy: Clonal plasma o Marrow failure (anemia, cells ≥10% thrombocytopenia) Imaging: o Immunosuppression (increased risk of infections) o X-rays or MRI: lytic bone lesions Renal impairment may occur due to o PET-CT: for detection of active light chain cast nephropathy lesions (myeloma kidney). Electrophoresis: Monoclonal spike (M spike) on SPEP/UPEP Free light chain assay: Elevated kappa or lambda light chains Differential Diagnosis Prognosis Monoclonal gammopathy of Highly variable; median survival undetermined significance 3-5 years with treatment (MGUS) Prognostic factors: serum β2- Waldenström’s microglobulin, cytogenetic macroglobulinemia abnormalities (e.g., t(4;14), del(17p)) Amyloidosis Treatment Initial treatment: o Immunomodulatory agents (thalidomide, lenalidomide) o Proteasome inhibitors (bortezomib) o Dexamethasone or other steroids Supportive care: o Bisphosphonates (to prevent bone disease) o Hydration and correction of hypercalcemia Autologous stem cell transplantation: in eligible patients Relapsed/Refractory disease: o Carfilzomib, pomalidomide, monoclonal antibodies (daratumumab) Radiation therapy: for localized bone pain or fractures Waldenström's Macroglobulinemia (WM) Definition Hepatosplenomegaly and A rare, slow-growing B-cell lymphadenopathy. lymphoma characterized by the Cold-induced Raynaud's overproduction of monoclonal IgM phenomenon or acrocyanosis. antibodies by lymphoplasmacytic May present with cells in the bone marrow. cryoglobulinemia and amyloidosis. Etiology Exact cause unknown; associated Diagnosis with MYD88 L265P mutation Serum protein electrophoresis (found in >90% of cases). (SPEP) and immunofixation: monoclonal IgM spike. Pathophysiology Bone marrow biopsy: lymphoplasmacytic infiltration. Abnormal B cells proliferate and produce excess IgM, leading to Peripheral blood smear: hyperviscosity, infiltration of bone rouleaux formation. marrow, and organ involvement. MYD88 mutation analysis. Increased serum viscosity in Clinical Features symptomatic patients. Hyperviscosity syndrome (due to high IgM levels): headaches, visual disturbances, dizziness, and bleeding. Neuropathy: due to cryoglobulins or amyloidosis. Anemia, fatigue, weight loss, night sweats. Differential Diagnosis Management Multiple myeloma. Asymptomatic patients: Chronic lymphocytic Observation. leukemia (CLL). Symptomatic patients: Other IgM-secreting Combination of conditions (e.g., IgM chemotherapy and myeloma). monoclonal antibodies. o Rituximab-based therapy (with or without Complications chemotherapy). Hyperviscosity syndrome o Plasmapheresis: for (requires urgent acute hyperviscosity plasmapheresis). symptoms. Cryoglobulinemia. o Bruton’s tyrosine Amyloidosis. kinase inhibitors (e.g., Secondary malignancies. Ibrutinib). o Stem cell transplant in younger or fit patients. Prognosis Slow progression, median survival ~5-10 years depending on disease burden and response to treatment.  Monoclonal Gammopathy of Undetermined Significance (MGUS) Definition Types A premalignant condition o Non-IgM MGUS: Most characterized by the presence of common; precursor to a monoclonal protein (M- multiple myeloma. protein) in the blood without o IgM MGUS: Precursor to evidence of malignant plasma Waldenström's cell disorder or end-organ macroglobulinemia. damage. o Light chain MGUS: Precursor Epidemiology to light chain multiple myeloma or AL amyloidosis. o Common in individuals over 50 years of age. o Incidence increases with age; Diagnostic Criteria around 3% of individuals over (International Myeloma Working 50 and 5% over 70 have Group): MGUS. o Serum monoclonal protein o Slight male predominance. (M-protein) < 3 g/dL. o Clonal bone marrow plasma Pathophysiology cells < 10%. o Monoclonal proliferation of o No evidence of CRAB criteria plasma cells, producing a (hyperCalcemia, Renal single type of failure, Anemia, Bone immunoglobulin (IgG, IgA, or lesions). IgM). o The condition may evolve into multiple myeloma, Waldenström’s macroglobulinemia, or amyloidosis. Clinical Features Management o Asymptomatic. o No specific treatment for o Detected incidentally MGUS. during evaluation for other o Regular monitoring (every conditions (e.g., routine 6-12 months) to detect blood tests). progression. o Assess for signs of end- Key Investigations organ damage (CRAB criteria). o Serum protein electrophoresis (SPEP) and immunofixation. Prognosis o Serum free light chain o Most patients remain assay. stable without o Bone marrow biopsy (if progression. needed to exclude other o Requires lifelong plasma cell disorders). monitoring due to the risk of transformation into malignancy. Risk of Progression o Approximately 1% per year risk of progression to multiple myeloma or related disorders. o Higher risk with elevated serum M-protein levels, abnormal free light chain ratio, and non-IgG MGUS.  Neutropenia Definition o Bone marrow disorders: Neutropenia is defined as an Aplastic anemia, leukemias, abnormally low concentration myelodysplastic syndromes of neutrophils (450 x 10^9/L). Long-term risk of progression to 2. Bone Marrow Findings: myelofibrosis or acute leukemia Increased megakaryocytes with is present but relatively low. normal maturation. 3. Exclusion of Other Summary Myeloproliferative Neoplasms: Absence of BCR- Essential Thrombocythemia is a ABL1 fusion gene, and not chronic myeloproliferative meeting criteria for disorder characterized by high polycythemia vera or primary platelet counts and potential myelofibrosis. thrombotic or hemorrhagic complications. Accurate diagnosis 4. Genetic Mutation: Presence of relies on clinical, laboratory, and JAK2 V617F, CALR, or MPL genetic criteria. Management mutations. focuses on reducing thrombotic risk and controlling platelet levels. Management Aspirin Therapy: Low-dose aspirin is often used to reduce thrombotic risk. Cytoreductive Therapy: Considered in high-risk patients (e.g., hydroxyurea, interferon alpha). Platelet-Reducing Agents: Anagrelide may be used to reduce platelet count in some cases. Monitoring: Regular follow-up to monitor platelet counts and assess for complications.  Myelofibrosis Definition Signs: A rare myeloproliferative o Anemia neoplasm characterized by the o Thrombocytopenia or replacement of bone marrow with thrombocytosis fibrous tissue. o Leukopenia or leukocytosis Pathophysiology Diagnosis Bone Marrow: Replacement of hematopoietic tissue with Blood Tests: collagenous fibrosis. o Complete Blood Count (CBC): Hemopoiesis: Extramedullary Anemia, leukocytosis, or hematopoiesis in the spleen leukopenia, and liver due to ineffective bone thrombocytopenia or marrow function. thrombocytosis. Genetics: Associated with o Peripheral Blood Smear: mutations in JAK2, MPL, and Leukoerythroblastic picture CALR genes. (presence of immature red and white blood cells). Bone Marrow Biopsy: Clinical Features o Hypercellularity with extensive Symptoms: fibrosis. o Fatigue Genetic Testing: o Weight loss o JAK2 V617F mutation is o Night sweats present in most cases. o Fever Imaging: o Splenomegaly (common) o Ultrasound or CT scan of the abdomen to assess spleen o Hepatomegaly and liver enlargement. Treatment Prognosis Symptomatic Management: Variable; dependent on age, o Blood transfusions for disease progression, and anemia. response to treatment. o Erythropoiesis-stimulating Survival: Median survival agents. varies widely, but prognosis can be poor without o JAK2 inhibitors (e.g., effective treatment. ruxolitinib) for symptom control and disease modification. Complications Splenectomy: Secondary: Increased risk o Considered in cases of of acute myeloid leukemia massive splenomegaly (AML) transformation. causing significant Additional Issues: symptoms. Increased risk of thrombotic Allogeneic Stem Cell events and bleeding due to Transplant: platelet dysfunction. o Considered in younger patients with high-risk Follow-Up disease. Regular monitoring of blood counts and symptoms. Periodic reassessment of treatment efficacy and side effects. Chronic Myeloid Leukemia (CML) Definition Clinical Features Chronic Myeloid Leukemia (CML) is a Symptoms: type of cancer that originates in the o Fatigue bone marrow and affects the blood. It is characterized by the overproduction of o Weight loss myeloid cells, a type of white blood cell. o Night sweats o Splenomegaly Epidemiology o Hepatomegaly Incidence: Rare, accounting for o Abdominal pain or fullness about 15-20% of all leukemias in adults. Laboratory Findings: Age: Primarily affects adults, with a o Elevated white blood cell count peak incidence in the 5th to 6th with a high percentage of decades of life. neutrophils and their precursors. Gender: Slightly more common in o Presence of basophils and men. eosinophils. o Low platelet count may occur. Pathophysiology Genetic Mutation: CML is Diagnosis associated with the Philadelphia Blood Smear: Shows a high number chromosome, which results from a of myeloid cells at various stages of translocation between maturation. chromosomes 9 and 22, creating the BCR-ABL fusion gene. Bone Marrow Biopsy: Hypercellularity with increased BCR-ABL Fusion Protein: This granulocyte precursors. tyrosine kinase promotes cell proliferation and inhibits apoptosis, Cytogenetic Testing: Detection of leading to the accumulation of the Philadelphia chromosome and myeloid cells. BCR-ABL fusion gene. Stages Prognosis 1. Chronic Phase: Chronic Phase: Good prognosis with appropriate TKI therapy. o Duration: Several years Accelerated/Blast Phase: Worse o Typically responds well to prognosis, requiring more treatment. intensive treatment. 2. Accelerated Phase: o Duration: Months Monitoring o Increasing symptoms and lab Regular Blood Tests: To monitor abnormalities. response to treatment and 3. Blast Crisis: disease progression. o Duration: Weeks Bone Marrow Biopsy: To assess o Resembles acute leukemia with response to therapy and detect high blast counts in blood and any transformation. bone marrow. Complications Treatment Disease Transformation: To Tyrosine Kinase Inhibitors (TKIs): acute leukemia. o First-line treatment (e.g., TKI Side Effects: Nausea, fatigue, Imatinib, Dasatinib, Nilotinib). liver enzyme abnormalities. o Effective in targeting the BCR- ABL protein. Follow-up Chemotherapy: Regular monitoring for treatment o Used in cases where TKIs are efficacy and side effects. not effective or in blast crisis. Assessment for potential disease Stem Cell Transplant: progression or transformation. o Considered for patients with accelerated phase or blast crisis, or those who do not respond to TKIs.  Myelodysplastic Syndromes (MDS) Definition Classification A group of clonal hematopoietic Based on number of dysplastic disorders characterized by lineages, cytopenias, and blast ineffective hematopoiesis, count. dysplasia in one or more myeloid o Common subtypes: cell lines, and a risk of transformation to acute myeloid ▪ MDS with single-lineage leukemia (AML). dysplasia (MDS-SLD) ▪ MDS with multilineage dysplasia (MDS-MLD) Etiology ▪ MDS with excess blasts o Primary (Idiopathic): Usually (MDS-EB) in older adults (median age ~70). ▪ MDS with isolated del(5q) o Secondary: Resulting from prior chemotherapy, Clinical Features radiation, or environmental o Cytopenias: Anemia (most toxins (e.g., benzene). common), neutropenia, thrombocytopenia. Pathophysiology o Symptoms of bone marrow o Bone marrow failure due to failure: Fatigue, infections, ineffective hematopoiesis easy bruising, and bleeding. and increased apoptosis. o Splenomegaly (in some o Clonal proliferation of cases). abnormal myeloid progenitors. o Risk of progression to AML. Diagnosis Management o Peripheral Blood Smear: o Supportive Care: Blood Macrocytic or normocytic transfusions, erythropoiesis- anemia, dysplastic features in stimulating agents, antibiotics white cells or platelets. for infections. o Bone Marrow Biopsy: o Disease-Modifying Hypercellular or hypocellular Therapies: marrow with dysplastic ▪ Hypomethylating agents myeloid precursors, blast (e.g., azacitidine, count 11 mg/dL). leads to bone destruction (lytic lesions) and impaired normal R: Renal insufficiency (serum hematopoiesis. creatinine >2 mg/dL). Overproduction of monoclonal A: Anemia (Hb 450,000/µL, JAK2, CALR, or acute leukemia. MPL mutations, exclusion of reactive thrombocytosis. Types o Treatment: Aspirin, 1.Polycythemia Vera (PV): hydroxyurea, anagrelide for high-risk patients. o Characteristics: Increased red blood cell mass, often associated with elevated white blood cells and platelets. 3.Primary Myelofibrosis (PMF): Complications o Characteristics: Bone marrow Thromboembolic events (PV, ET). fibrosis leading to cytopenias, Transformation to acute extramedullary hematopoiesis. leukemia. o Clinical Features: Myelofibrosis progression (ET, Splenomegaly, fatigue, weight PV). loss, night sweats, anemia, bone pain. Prognosis o Diagnosis: Leukoerythroblastic blood smear, bone marrow Highly variable depending on the fibrosis, JAK2, CALR, or MPL specific MPN subtype and mutations. mutation status. o Treatment: Ruxolitinib (JAK2 PV and ET generally have a inhibitor), blood transfusions, favorable prognosis with proper allogeneic stem cell transplant management, while PMF carries a (in selected cases). worse prognosis due to progressive fibrosis and transformation risks. 4.Chronic Myeloid Leukemia (CML): Monitoring o Characteristics: BCR-ABL Regular CBC, bone marrow biopsy fusion gene (Philadelphia (if indicated), JAK2, CALR, MPL chromosome), resulting in mutation tracking. uncontrolled myeloid proliferation. Risk stratification based on age, history of thrombosis, and o Clinical Features: Fatigue, cytogenetic abnormalities. weight loss, splenomegaly, elevated white blood cell count. o Diagnosis: Presence of BCR- ABL fusion gene by PCR or FISH. o Treatment: Tyrosine kinase inhibitors (e.g., imatinib), allogeneic stem cell transplant (in refractory cases).  Transfusion 7 Medicine Transfusion Reactions o Hemolytic Transfusion Reactions o Febrile Non-Hemolytic Transfusion Reactions o Allergic Transfusion Reactions o Transfusion-Related Acute Lung Injury (TRALI) o Transfusion-Associated Circulatory Overload (TACO) Blood Component Therapy o Red Blood Cell Transfusion o Platelet Transfusion o Plasma Transfusion o Cryoprecipitate Transfusion Hemolytic Transfusion Reactions Definition o Symptoms: Mild fever, jaundice, Hemolytic transfusion reactions (HTRs) anemia, hemoglobinuria, indirect occur when transfused red blood cells hyperbilirubinemia. (RBCs) are destroyed by the recipient's o Management: Supportive care, immune system, either intravascularly transfusion of antigen-negative or extravascularly. blood for future transfusions. Types Acute Hemolytic Transfusion Diagnosis Reaction (AHTR): Lab Tests: o Onset: Within minutes to 24 hours o Positive direct antiglobulin test after transfusion. (DAT/Coombs test) o Mechanism: ABO incompatibility, o Increased lactate dehydrogenase leading to complement activation (LDH) and intravascular hemolysis. o Decreased haptoglobin o Symptoms: Fever, chills, hypotension, chest pain, back o Hemoglobinuria pain, dyspnea, hemoglobinuria, o Hyperbilirubinemia shock, disseminated intravascular coagulation (DIC), renal failure. o Management: Immediate Prevention cessation of transfusion, Proper blood typing and cross- supportive care, fluid resuscitation, matching. and management of DIC or renal Monitoring and screening for failure. antibodies in high-risk patients (e.g., those with prior transfusions or Delayed Hemolytic Transfusion pregnancies). Reaction (DHTR): o Onset: Days to weeks after transfusion. Complications o Mechanism: Anamnestic response Acute renal failure, DIC, shock, to non-ABO antibodies (e.g., Rh, multiorgan failure (in severe AHTR). Kell), causing extravascular hemolysis.  Febrile Non-Hemolytic Transfusion Reactions (FNHTRs) Definition Management FNHTRs are immune-mediated Stop transfusion immediately. transfusion reactions characterized by Administer antipyretics (e.g., fever and chills, occurring within 1-6 acetaminophen). hours of transfusion, without hemolysis. Monitor the patient closely. Rule out bacterial contamination or Pathophysiology hemolysis. Caused by recipient antibodies reacting to donor leukocytes or Prevention cytokines accumulated in stored blood products. Leukoreduction of blood products (removal of white blood cells). Cytokine release (e.g., IL-1, IL-6, TNF) from leukocytes during blood Use of fresher blood products to storage is a major contributor. minimize cytokine buildup. Clinical Features Prognosis Fever (rise in body temperature by Generally mild, self-limited, and ≥1°C or 2°F) non-life-threatening. Chills, rigors Recurrence possible in future transfusions. Mild dyspnea Headache, malaise Key Points Diagnosis Most common transfusion reaction. Exclusion of other transfusion Does not involve hemolysis or severe reactions (e.g., hemolytic, septic, complications. allergic) Prevention strategies reduce Negative direct antiglobulin test incidence. (DAT) Absence of hemolysis (normal haptoglobin, LDH, bilirubin)  Allergic Transfusion Reactions Definition Pathophysiology o Allergic reactions to blood o Immune response triggered by transfusions are immune- donor plasma proteins or other mediated responses to plasma allergens in the transfused proteins or other components blood. in transfused blood products. o In severe cases, IgA-deficient o Can range from mild (urticaria) individuals can react to IgA in to severe (anaphylaxis). donor plasma. Types Clinical Features Mild Allergic Reaction: o Mild: Itching, hives, erythema, flushing. ▪ Characterized by itching, hives (urticaria), or rash. o Severe: Wheezing, hypotension, respiratory ▪ Occurs in 1-3% of distress, shock. transfusions. Severe Allergic Reaction (Anaphylaxis): ▪ Rare but life-threatening. ▪ Symptoms include hypotension, bronchospasm, and angioedema. ▪ Associated with IgA deficiency or sensitivity to plasma proteins. Diagnosis Prevention o Based on clinical o Premedication with presentation during or antihistamines for patients shortly after transfusion. with a history of mild allergic o Rule out other causes of reactions. transfusion reactions (e.g., o Use of washed red blood hemolytic reactions, TRALI). cells or plasma-reduced components in individuals with recurrent or severe Management reactions, particularly in IgA Mild Reaction: deficiency. ▪ Stop transfusion temporarily. Prognosis ▪ Administer antihistamines o Mild reactions are self- (e.g., diphenhydramine). limiting. ▪ Resume transfusion once o Severe reactions, though symptoms resolve. rare, can be fatal if not Severe Reaction: treated promptly. ▪ Immediately stop transfusion. ▪ Administer epinephrine, corticosteroids, and antihistamines. ▪ Provide supportive care (oxygen, fluids).  Transfusion-Related Acute Lung Injury (TRALI) Definition Clinical Features A serious, life-threatening Acute onset of respiratory complication of blood distress, dyspnea, transfusion characterized by hypoxemia. acute non-cardiogenic Bilateral pulmonary pulmonary edema occurring infiltrates on chest X-ray. within 6 hours of transfusion. Fever, hypotension, and tachycardia may be present. Etiology Symptoms typically occur Likely immune-mediated. within 1-2 hours of Anti-HLA or anti-HNA transfusion, up to a (human neutrophil antigen) maximum of 6 hours. antibodies present in donor plasma react with recipient Diagnosis leukocytes, leading to neutrophil activation and Based on clinical lung injury. presentation and exclusion of other causes of acute lung injury (e.g., volume Risk Factors overload, cardiac Plasma-rich blood products dysfunction, infections). (e.g., FFP, platelets). Diagnostic criteria include Multiparous female donors acute onset of hypoxemia are more likely to have and new infiltrates on chest antibodies that can cause imaging without evidence of TRALI. circulatory overload. Management Prognosis Immediate cessation of Mortality rate ranges from 5- transfusion. 10%. Supportive care: oxygen Most patients recover with supplementation, appropriate supportive care mechanical ventilation if within 48-96 hours. required. Avoid diuretics as the Differential Diagnosis mechanism is non- cardiogenic. Transfusion-associated circulatory overload (TACO). Fluid management should be conservative. Acute respiratory distress syndrome (ARDS). Sepsis. Prevention Minimize unnecessary transfusions. Use male donor plasma or exclude multiparous females from plasma donation to reduce risk.  Transfusion-Associated Circulatory Overload (TACO) Definition Clinical Features TACO is a transfusion-related Dyspnea, orthopnea, cough. complication characterized by acute onset of circulatory Hypertension, tachycardia. overload due to excessive blood Jugular venous distension (JVD). volume infused, leading to Pulmonary edema (bilateral respiratory distress and heart lung crackles). failure. Hypoxemia (low oxygen saturation). Etiology Signs of heart failure (S3 Large volume transfusions or gallop). rapid transfusion rates. Underlying conditions: Cardiac, renal impairment, or elderly patients. Positive fluid balance (multiple transfusions in a short time). Risk Factors Age extremes (elderly, infants). Pre-existing heart disease, chronic kidney disease (CKD). Multiple transfusions or rapid transfusions. Large volume of transfusion (especially plasma, platelets). Diagnosis Prevention Clinical assessment of fluid Slow transfusion rates, overload. especially in high-risk Chest X-ray: Pulmonary patients. edema, cardiomegaly. Pre-transfusion diuretics in Elevated brain natriuretic at-risk patients. peptide (BNP). Monitor fluid status closely Echocardiogram: Cardiac during transfusions. dysfunction. Complications Management Acute respiratory distress Stop transfusion syndrome (ARDS). immediately. Prolonged hospitalization. Oxygen therapy. Diuretics (e.g., furosemide) Prognosis to reduce fluid overload. Most cases resolve with Supportive care: Fluid appropriate management, restriction. but severe cases can lead to Monitor vitals and fluid significant morbidity. balance. Red Blood Cell (RBC) Transfusion Indications Preparation Symptomatic anemia (e.g., Blood typing and cross- fatigue, dyspnea, matching (ABO and Rh tachycardia). compatibility). Acute blood loss with Leukoreduced blood is hemodynamic instability. preferred to minimize febrile Chronic anemia reactions and unresponsive to other alloimmunization. treatments (e.g., refractory Irradiated blood for to iron, B12, or folate immunocompromised therapy). patients to prevent graft- Hemoglobin threshold versus-host disease. typically: o