HEMA LEC - midterm bone marrow to hemolysis

Pancytopenia

Reduction of RBCs, WBCs, and platelets.

Bone marrow failure

Reduction or cessation of blood cell production affecting one or more cell lines.

6 Mechanisms of Bone Marrow Failure

HSC destruction; premature HSC senescence/apoptosis; ineffective hematopoiesis; marrow microenvironment disruption; decreased growth factor production; marrow infiltration.

Aplastic anemia

Pancytopenia, reticulocytopenia, and hypocellular bone marrow due to defective or depleted hematopoietic stem cells.

Acquired Aplastic Anemia Triggers

Drugs, benzene and other toxic chemicals, radiation, viral infections, and autoimmune stem cell destruction.

Viruses Causing Aplastic Anemia

EBV, non-A/non-B/non-C/non-G hepatitis viruses, and HIV.

CD55 (DAF)

Decay Accelerating Factor; protects blood cells from complement destruction.

CD59 (MIRL)

Membrane Inhibitor of Reactive Lysis; prevents membrane attack complex formation.

Ham Acidified Serum Test

Older diagnostic test for complement-mediated hemolysis in PNH.

Aplastic Anemia Treatment Under 40

Hematopoietic stem cell transplantation from an HLA-identical sibling.

Aplastic Anemia Treatment Over 40 or No HLA Match

Antithymocyte globulin (ATG) plus cyclosporine.

Fanconi Anemia

Most common inherited aplastic anemia; characterized by chromosomal instability and fragile chromosomes.

Fanconi Anemia Physical Findings

Thumb/skeletal malformations, café-au-lait pigmentation, short stature, and eye, kidney, or genital abnormalities.

Fanconi Anemia Diagnostic Markers

Pancytopenia, macrocytosis, elevated HbF, increased AFP, and chromosome fragility.

Dyskeratosis Congenita (DKC)

Inherited bone marrow failure due to telomere maintenance defects.

Dyskeratosis Congenita Triad

Abnormal skin pigmentation, dystrophic nails, and oral leukoplakia.

Shwachman-Diamond Syndrome (SDS)

Inherited disorder characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal dysplasias.

Shwachman-Diamond Syndrome Treatment

G-CSF, pancreatic enzyme replacement, transfusion support, and allogeneic BMT when indicated.

Pure Red Cell Aplasia (PRCA)

Severe reduction in RBC precursors with normal WBCs and platelets.

Transient Erythroblastopenia of Childhood (TEC)

Temporary acquired PRCA in young children following a viral infection.

Diamond-Blackfan Anemia (DBA)

Congenital erythroid hypoplasia caused by ribosomal protein gene mutations; presents with macrocytic anemia and reticulocytopenia.

Congenital Dyserythropoietic Anemia (CDA)

Inherited anemia characterized by ineffective erythropoiesis, reticulocytopenia, and dysplastic erythroblasts.

CDA Type I

Megaloblastoid erythroblasts with internuclear chromatin bridges and Swiss Cheese heterochromatin.

CDA Type II (HEMPAS)

Most common CDA subtype; Hereditary Erythroblast Multinuclearity with Positive Acidified Serum test.

CDA Type III

Least common subtype of congenital dyserythropoietic anemia.

Myelophthisic Anemia

Anemia caused by bone marrow infiltration by abnormal or malignant cells.

Leukoerythroblastic Smear

Peripheral smear showing immature myeloid cells and nucleated RBCs; characteristic of myelophthisic anemia.

Dacryocytes

Teardrop-shaped RBCs associated with infiltrated, overcrowded bone marrow.

Anemia of Chronic Kidney Disease

Anemia primarily caused by inadequate erythropoietin production by damaged kidneys.

Burr Cells (Echinocytes)

RBCs with short, uniform, evenly spaced projections; characteristic of uremia.

Intrinsic Hemolysis

RBC destruction caused by defects within the RBC, such as membrane defects, enzymopathies, and hemoglobinopathies.

Extrinsic Hemolysis

RBC destruction caused by external factors, such as antibodies, microangiopathic trauma, malaria, and chemical toxins.

Intravascular Hemolysis

RBC destruction occurring directly inside blood vessels.

Extravascular Hemolysis

RBC destruction by macrophages, primarily in the spleen and liver.

Splenic Pitting

Removal of damaged RBC membrane portions by splenic macrophages, producing spherocytes.

Spherocytes

Spherical RBCs lacking central pallor, associated with extravascular hemolysis.

Schistocytes

Fragmented RBCs caused by mechanical shearing; characteristic of intravascular hemolysis.

Reticulocytosis

Increased immature RBC count as a bone marrow response to peripheral hemolysis.

Polychromasia

Bluish-gray RBCs on a smear due to residual RNA in reticulocytes.

Erythroid Hyperplasia

Compensatory expansion of bone marrow RBC precursors during hemolytic anemia.

Heme Oxygenase

Enzyme that converts heme into biliverdin and carbon monoxide.

Biliverdin Reductase

Enzyme that converts biliverdin into unconjugated bilirubin.

Unconjugated Bilirubin (B1 / Indirect)

Water-insoluble bilirubin that binds albumin for transport to hepatocytes.

Ligandin (Z Protein)

Intracellular hepatic protein that transports unconjugated bilirubin within hepatocytes.

Glucuronyl Transferase

Hepatic enzyme that conjugates bilirubin with glucuronic acid.

Conjugated Bilirubin (B2 / Direct)

Water-soluble bilirubin excreted into bile and the small intestine.

Urobilinogen

Intestinal metabolite of conjugated bilirubin that may be reabsorbed or excreted in urine and feces.

Stercobilin

Oxidized product of urobilinogen responsible for the brown color of stool.

Urobilin

Oxidized product of urobilinogen responsible for the yellow color of urine.

Pre-hepatic (Hemolytic) Jaundice

Jaundice with increased unconjugated bilirubin and urinary urobilinogen.

Haptoglobin

Plasma protein that binds free hemoglobin during intravascular hemolysis; serum levels decrease.

Hemopexin

Salvage protein that binds free metheme when haptoglobin is depleted and delivers it to the liver.

Methemalbumin

Complex formed when excess metheme binds albumin after haptoglobin and hemopexin are saturated.

Hemoglobinuria

Free hemoglobin in urine when intravascular hemolysis exceeds plasma binding and renal reabsorption capacity.