All Blood Conditions: Anemias, Hemostasis, and Malignancies

Comprehensive flashcards covering the pathophysiology, clinical presentations, diagnostic criteria, and laboratory hallmarks of hematological conditions including anemias, hemostasis/thrombophilia disorders, and hematological malignancies.

Iron Deficiency Anemia

A microcytic, hypochromic anemia caused by inadequate dietary intake, gastric sleeve surgery, or chronic blood loss (e.g., peptic ulcers, colon cancer, hookworm). Clinical features include pica, brittle nails, and koilonychia (spoon-shaped nails). Laboratory evaluation demonstrates decreased ferritin, increased transferrin, increased TIBC, and a peripheral blood smear showing pencil cells (elliptocytes) and target cells.

Anemia of Chronic Disease

A normocytic or microcytic anemia mediated by inflammatory cytokines such as $IL\text{-}6$, which stimulates hepatic synthesis and release of hepcidin to sequester iron. Laboratory findings show normal to elevated ferritin, and treatment includes administration of erythropoietin.

Aplastic Anemia

A bone marrow failure syndrome characterized by peripheral pancytopenia, marked bone marrow hypocellularity, and an absence of reticulocytes; causes may be idiopathic or secondary to exposure to radiation or drugs.

Megaloblastic Anemia

A macrocytic, hyperchromic anemia resulting from vitamin $B_{12}$ or folate deficiency. Hallmark findings include hypercellular bone marrow, macro-ovalocytes, hypersegmented neutrophils, target cells, reticulocytopenia, leukopenia, thrombocytopenia, and elevated serum iron, ferritin, and unconjugated bilirubin. Clinical signs include glossitis, angular stomatitis, cheilitis, and peripheral neuropathy (specific to $B_{12}$ deficiency).

Pernicious Anemia

An autoimmune form of megaloblastic anemia caused by the autoimmune destruction of gastric parietal cells and intrinsic factor (IF). Classic signs include a red beefy tongue, early graying of hair, vitiligo, and gastric atrophy.

Warm Autoimmune Hemolytic Anemia

An extravascular hemolytic anemia mediated by $IgG$ autoantibodies that react at body temperature ($37^\text{o}\text{C}$). Patients present with jaundice, hepatomegaly, elevated $LDH$, indirect hyperbilirubinemia, reticulocytosis, spherocytes on blood film, and a positive direct antiglobulin test ($DAT^+$).

Cold Autoimmune Hemolytic Anemia

An autoimmune hemolytic anemia mediated by $IgM$ antibodies that bind red blood cells at lower temperatures; typically presents with intravascular or extravascular hemolysis and frequently develops following Mycoplasma pneumoniae infection or infectious mononucleosis.

Paroxysmal Nocturnal Hemoglobinuria (PNH)

An acquired stem cell disorder caused by a deficiency of GPI-anchored surface proteins, specifically $CD55$ and $CD59$. This leads to unregulated complement-mediated intravascular lysis of red blood cells, producing episodic dark morning urine (hemoglobinuria worst at night).

Hereditary Spherocytosis (Spirocytosis)

An inherited red blood cell membranopathy caused by a vertical cytoskeletal linkage defect in ankyrin. Characterized by spherocytes, anemia, splenomegaly, pigment gallstones, elevated indirect bilirubin, elevated $LDH$, increased RBC osmotic fragility, and a negative DAT; patients are at risk for an acute aplastic crisis when infected with Parvovirus B19.

Hereditary Elliptocytosis

An inherited red blood cell membranopathy caused by a horizontal skeletal defect involving $\alpha$-spectrin and band 4.1, leading to oval or pencil-shaped red blood cells on the peripheral blood smear.

Hereditary Pyropoikilocytosis

A severe hemolytic membranopathy subtype characterized by marked erythrocyte morphological abnormalities caused by an intrinsic defect in the multimerization of spectrin.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

An X-linked recessive RBC enzymopathy in which an impaired pentose phosphate pathway produces insufficient $NADPH$, preventing glutathione reductase from maintaining reduced glutathione for $ROS$ detoxification. Oxidative stress leads to acute intravascular hemolysis, hemoglobinuria, and blood films demonstrating bite cells, Heinz bodies, and blister cells.

HbH Disease

A form of $\alpha$-thalassemia resulting from deletion or loss of function of 3 $\alpha$-globin genes, leading to an excess of $\beta$-chains that aggregate into unstable $\beta_4$ homotetramers.

Hb Bart's Disease

The most severe form of $\alpha$-thalassemia caused by the absence of all 4 $\alpha$-globin genes, resulting in excess fetal $\gamma$-globin chains aggregating into $\gamma_4$ homotetramers, causing hydrops fetalis.

$\beta$-Thalassemia Minor (Trait)

A heterozygous $\beta$-globin chain deficiency characterized by microcytosis, hypochromia, normal total hemoglobin, elevated $HbA_2$, and a peripheral smear revealing basophilic stippling and target cells.

$\beta$-Thalassemia Major

A severe hemoglobinopathy characterized by absent or severely reduced $\beta$-globin synthesis and markedly elevated $HbF$. Manifests with growth retardation, hepatosplenomegaly, thalassemic facies, 'hair-on-end' skull radiographic appearance, and pigment gallstones; roughly half of affected individuals carry the $HbE/\beta^0$ genotype.

Sickle Cell Disease (SCD)

An autosomal recessive hemoglobinopathy caused by a point mutation in the $\beta$-globin gene ($\text{Glu6Val}$ substitution, producing $\beta^S$). Characterized by normocytic anemia, dehydration-induced vaso-occlusive crises, leg ulcers, pigment gallstones, aplastic crises secondary to Parvovirus B19 infection, and autosplenectomy leading to Howell-Jolly bodies; treated with hydroxyurea to elevate $HbF$.

Immune Thrombocytopenia Purpura (ITP)

An autoimmune disorder of primary hemostasis typically affecting young women in their 20s, characterized by isolated thrombocytopenia ($\pm$ anemia), generalized cutaneous bruising, absence of splenomegaly, completely normal coagulation panels ($PT$ and $APTT$), and normal red blood cell morphology.

Thrombotic Thrombocytopenia Purpura (TTP)

A microangiopathic hemolytic disorder caused by a deficiency in the von Willebrand factor cleaving protease $ADAMTS13$. Characterized by widespread platelet microthrombi, consumptive thrombocytopenia, anemia, intravascular hemolysis with schistocytes, and normal coagulation times ($PT$ and $APTT$).

Disseminated Intravascular Coagulation (DIC)

A severe consumptive coagulopathy affecting both primary and secondary hemostasis, commonly precipitated by gram-negative bacterial sepsis or obstetric complications. Characterized by systemic consumption of platelets, fibrinogen, coagulation factors, anticoagulants, and red blood cells, resulting in elevated D-dimers, schistocytes, and prolongation of $PT$, $APTT$, and $TT$.

Bernard-Soulier Syndrome (BSS)

A hereditary qualitative platelet disorder (thrombocytopathy) caused by a defect in glycoprotein $Ib$ ($GP1B$), which impairs platelet adhesion to exposed subendothelial von Willebrand factor.

Glanzmann's Thrombasthenia (GT)

A hereditary qualitative platelet disorder caused by a defect in the glycoprotein $IIb/IIIa$ ($GPIIb\text{-}IIIa$) integrin complex, preventing fibrinogen cross-linking and platelet aggregation.

Von Willebrand Disease (vWF Disease)

The most common inherited bleeding disorder, affecting both primary hemostasis (platelet adhesion) and secondary hemostasis (Factor VIII protection). Divided into Type 1 (quantitative deficiency), Type 2 (qualitative defect: 2A with decreased vWF multimers, 2B with increased platelet binding, 2M with decreased platelet binding, 2N with decreased Factor VIII binding), and Type 3 (complete deficiency).

Hemophilia

An X-linked inherited secondary hemostatic disorder characterized by deep tissue hematomas, hemarthrosis, and an isolated prolonged $APTT$ with a normal $PT$. Subdivided into Hemophilia A (deficiency of Factor $VIII$) and Hemophilia B (deficiency of Factor $IX$).

Vitamin K Deficiency

A coagulopathy resulting from defective enzymatic $\gamma$-carboxylation of coagulation factors $II$, $VII$, $IX$, and $X$, resulting in prolongation of both $PT$ and $APTT$; commonly manifests as neonatal bleeding and represents the pharmacologic target of warfarin antagonism.

Factor XIII Deficiency

A rare inherited coagulation defect wherein patients present with deep and delayed bleeding episodes despite normal routine coagulation screening tests ($PT$ and $APTT$ are normal).

Excessive Fibrinolysis

A bleeding diathesis caused by unrestrained plasmin activity, inherited via deficiencies in key regulatory proteins such as decreased $\alpha_2$-antiplasmin or plasminogen activator inhibitor-1 ($PAI\text{-}1$) deficiency.

Factor V Leiden

The most common hereditary thrombophilia and leading cause of deep vein thrombosis ($DVT$); caused by a gain-of-function mutation ($\text{Arg506Glu}$) that makes Factor V resistant to cleavage and inactivation by activated protein C ($APC$ resistance), significantly increasing thrombosis risk during pregnancy or oral contraceptive use.

Prothrombin G20210A Mutation

A thrombophilic gain-of-function mutation involving a $G \rightarrow A$ nucleotide substitution at codon 20210 in the $3'\text{UTR}$ of the prothrombin (Factor II) gene, leading to elevated plasma prothrombin levels and increased risk for both venous and arterial thromboembolism.

Protein C Deficiency

A hereditary thrombophilia characterized by impaired inactivation of coagulation factors $V$ and $VIII$. Physiologically, Protein C is activated on endothelial surfaces by the thrombin-thrombomodulin complex.

Hyperhomocysteinemia

An elevation of circulating homocysteine associated with an increased risk of venous and arterial thrombosis; most commonly caused by deficiencies in vitamin $B_{12}$ or folate, or by genetic deficiency of methylenetetrahydrofolate reductase ($MTHFR$).

Anti-phospholipid Antibodies (Lupus Anticoagulant)

An acquired autoimmune thrombophilia often seen in patients with systemic lupus erythematosus ($SLE$) (associated with malar butterfly rash, glomerulonephritis, and arthralgia); clinically manifests with venous thrombosis and recurrent miscarriages, and classically shows an in vitro prolonged $APTT$ with a normal $PT$.

Myelodysplastic Syndrome (MDS)

A clonal pre-leukemic bone marrow disorder characterized by ineffective hematopoiesis and $< 20\%$ blasts. Peripheral findings include pancytopenia, elevated $MCV$, macro-ovalocytes, basophilic stippling, and hypo-/hyper-lobulated, hypogranulated neutrophils; bone marrow is hypercellular with nuclear budding, ring sideroblasts, and micromegakaryocytes.

Acute Myeloid Leukemia (AML)

An aggressive hematologic malignancy characterized by $\ge 20\%$ myeloblasts in bone marrow or peripheral blood, often containing Auer rods. Symptoms include severe fatigue, pancytopenia, gingival hypertrophy, and hepatosplenomegaly. Positive for myeloid flow cytometry markers ($MPO$, $CD13$, $CD33$) and associated with cytogenetic rearrangements like $t(8;21)$, $t(15;17)$, and $inv(16)$.

Chronic Myeloid Leukemia (CML)

A myeloproliferative neoplasm driven by the Philadelphia chromosome translocation $t(9;22)$, forming the $BCR\text{-}ABL$ fusion gene that constitutively increases tyrosine kinase activity; manifests with marked granulocytic leukocytosis and basophilia.

Polycythemia Vera (PV)

A myeloproliferative neoplasm characterized by bone marrow panmyelosis and increased erythrocytosis (elevated $Hb$ and hematocrit). Driven by the $JAK2$ mutation and presenting clinically with a plethoric (red) face, pruritus (itching), hepatosplenomegaly, and headache.

Essential Thrombocythemia (ET)

A chronic myeloproliferative disorder characterized by marked sustained thrombocytosis, splenomegaly, painful burning extremities (erythromelalgia), and thrombosis; driven by mutations in $JAK2$ and calreticulin.

Primary Myelofibrosis

A myeloproliferative neoplasm characterized by progressive reactive marrow fibrosis replacing normal hematopoietic tissue; peripheral blood smear displays a classic leukoerythroblastic picture with nucleated RBCs, left-shifted immature white blood cells, and tear drop cells (dacrocytes).

Acute Lymphoblastic Leukemia (ALL)

An aggressive hematologic malignancy primarily affecting pediatric patients, presenting with peripheral cytopenias, bone and joint pain, testicular swelling, and systemic B-symptoms; blasts express terminal deoxynucleotidyl transferase ($TdT$) alongside lineage-specific markers (B-cell: $CD10$, $CD19$, $CD20$; T-cell: $CD3$, $CD5$, $CD7$).

Chronic Lymphocytic Leukemia (CLL)

An indolent clonal B-cell malignancy presenting with absolute lymphocytosis, smudge cells on peripheral smear, lymphadenopathy, hepatosplenomegaly, hypogammaglobulinemia, and occasionally secondary autoimmune hemolytic anemia with spherocytes.

Hodgkin Lymphoma

A lymphoid malignancy defined pathognomonically by binucleated Reed-Sternberg cells with prominent nucleoli ('owl-eye' appearance) that express $CD15$ and $CD30$. Typical presentation includes cervical and mediastinal lymphadenopathy, pruritus, and localized pain within affected lymph nodes following alcohol consumption.

Diffuse Large B-Cell Lymphoma (DLBCL)

The most common Non-Hodgkin Lymphoma subtype; characterized as a clinically aggressive, highly symptomatic, high-grade neoplasm composed of large atypical B cells expressing $CD20$.

Follicular Lymphoma (FL)

An indolent Non-Hodgkin B-cell lymphoma characterized histologically by crowded, back-to-back lymphoid follicles in the lymph node, driven by the chromosomal translocation $t(14;18)$ that leads to overexpression of the anti-apoptotic protein $Bcl\text{-}2$ in $CD20^+$ cells.

Burkitt Lymphoma

A highly aggressive Non-Hodgkin B-cell lymphoma presenting with facial, jaw, or abdominal masses and B-symptoms; characterized by a 'starry sky' histological appearance and the chromosomal translocation $t(8;14)$, which juxtaposes $c\text{-}myc$ with the Ig heavy chain locus.

Multiple Myeloma

A plasma cell dyscrasia characterized by the CRAB tetrad: hypercalcemia ($\uparrow Ca$), renal impairment (elevated urea and creatinine), anemia, and osteolytic bone lesions causing severe bone pain. Diagnostic features include a monoclonal paraprotein serum M-spike, Bence Jones proteinuria, rouleaux formation of red blood cells, and heightened susceptibility to infections.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

An asymptomatic plasma cell dyscrasia characterized by the detection of a serum M-spike and mild bone marrow plasmacytosis ($< 10\%$) without evidence of end-organ CRAB manifestations.

Plasmacytoma

A discrete, solitary localized tumor mass composed exclusively of neoplastic monoclonal plasma cells occurring in the absence of systemic CRAB features.

Primary Amyloidosis

A plasma cell disorder characterized by the extracellular deposition of monoclonal immunoglobulin light-chain amyloid fibrils, leading to organomegaly (such as macroglossia and cardiomegaly); diagnosed via Congo red staining demonstrating pathognomonic apple-green birefringence under polarized light.