I have propaedeutics practicle exam in department hematology so give me all possible information that need to be known to me to get grade 9 or 10

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This is your complete hematology propaedeutics exam guide. Here is a quick orientation to how it's structured:

What's Covered (10 Parts)

Part	Topic
1	History-taking: chief complaints, key questions
2	Physical examination: pallor, lymph nodes (all stations), splenomegaly grading, sternal tenderness
3	CBC interpretation: normal values, MCV classification, reticulocyte count, WBC differential
4	Peripheral blood smear: all red cell morphologies and their diseases
5	Major diseases: anemias, polycythemia, leukemias, lymphomas, myeloma, MDS, MPNs, bleeding disorders
6	Bone marrow: indications, technique, cellularity, M:E ratio
7	Key lab findings table for every major condition
8	Special tests (Coombs, flow cytometry, ADAMTS13, SPEP, etc.)
9	Blood transfusion: ABO/Rh, transfusion reactions and their mechanisms
10	Practical exam sequence + "spot diagnoses" examiners love

High-Priority Topics for a Practical Exam

For a propaedeutics practical (clinical skills exam), focus heavily on:

Physical exam technique for lymph nodes and spleen (examiner will ask you to demonstrate)
Recognizing peripheral smear findings (spherocytes, schistocytes, blasts, hypersegmented neutrophils, smudge cells)
Interpreting a CBC and naming the type of anemia from MCV + reticulocyte count
The classic "spot diagnoses" in Part 10 - these are very likely to appear
CRAB criteria for myeloma and B symptoms for lymphoma
Distinguishing TTP from DIC (normal vs. abnormal PT/APTT)
Iron deficiency vs. ACD lab patterns (the TIBC is the key differentiator)

Good luck on your exam!

I need all the disorders seen in this hematology department and their mechanisms only

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I now have sufficient depth from the textbooks. Let me compile the focused mechanisms-only guide.

Hematology Department Disorders - Mechanisms Only

Sources: Robbins & Kumar Pathologic Basis of Disease, Robbins Basic Pathology, Harrison's Principles of Internal Medicine 22E, Goldman-Cecil Medicine

I. ANEMIAS

1. Iron Deficiency Anemia

Mechanism: Iron is regulated by hepcidin (liver peptide). Hepcidin degrades ferroportin, the only iron exporter on enterocytes and macrophages. When body iron is depleted:

Hepcidin falls -> ferroportin upregulated -> more duodenal absorption
But when supply is insufficient (poor intake, chronic blood loss, malabsorption), stores are exhausted
Without iron, protoporphyrin cannot bind iron to form heme, and heme cannot combine with globin -> deficient hemoglobin synthesis -> microcytic hypochromic RBCs
Cells become smaller because each division produces less hemoglobin per cell

2. Anemia of Chronic Disease (ACD)

Mechanism: Inflammatory cytokines (IL-1, IL-6, TNF) from chronic infections, cancer, or autoimmune disease:

IL-6 upregulates hepcidin in the liver
Excess hepcidin degrades ferroportin on macrophages -> iron trapped inside macrophages and cannot be released to transferrin
Simultaneously, inflammatory cytokines suppress EPO production and blunt EPO receptor sensitivity on erythroid progenitors
Result: functional iron deficiency - iron is present in the body but unavailable for red cell production

3. Megaloblastic Anemia (B12 / Folate Deficiency)

Mechanism: Both B12 and folate are required for the synthesis of thymidylate (deoxythymidine monophosphate, a DNA building block):

Folate as methylenetetrahydrofolate donates a methyl group to uracil to make thymine
B12 is required to regenerate active THF from methyl-THF (the methyl trap hypothesis)
Without adequate thymidylate, DNA synthesis is impaired while RNA and protein synthesis continue normally
Nuclear maturation lags behind cytoplasmic growth -> megaloblasts (large cells with immature-looking nuclei and abundant cytoplasm)
Ineffective hematopoiesis: many megaloblasts die in the marrow before release (intramedullary hemolysis)
B12 also specifically required for conversion of methylmalonyl-CoA to succinyl-CoA; deficiency -> methylmalonyl-CoA accumulates -> incorporated into abnormal fatty acids -> myelin sheath damage (subacute combined degeneration)

4. Hemolytic Anemias

a. Hereditary Spherocytosis

Mechanism: Autosomal dominant mutations in spectrin, ankyrin, band 3, or protein 4.2 - proteins that anchor the lipid bilayer to the cytoskeleton. Without this anchorage, portions of membrane lipid vesiculate off -> the cell loses surface area while retaining volume -> becomes a sphere (least surface area for a given volume). Spherocytes are rigid, cannot deform through the splenic sinusoids, and are destroyed by splenic macrophages (extravascular hemolysis).

b. G6PD Deficiency

Mechanism: X-linked defect in glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate (HMP) shunt. G6PD generates NADPH, which maintains glutathione in its reduced form. Reduced glutathione protects hemoglobin from oxidative damage. Without NADPH:

Oxidative stress (infections, fava beans, drugs like primaquine, dapsone) causes oxidation of hemoglobin -> denatured hemoglobin precipitates as Heinz bodies -> Heinz bodies bind to membrane -> macrophages "bite" them out (bite cells) -> membrane damage -> intravascular and extravascular hemolysis
Older RBCs most vulnerable because G6PD activity declines with cell age

c. Autoimmune Hemolytic Anemia (AIHA) - Warm Type

Mechanism: IgG autoantibodies (active at 37°C) bind to antigens on the RBC surface (usually Rh antigens). IgG-coated RBCs are recognized by Fc receptors on splenic macrophages -> partial or complete phagocytosis. Partial phagocytosis removes membrane without removing contents -> spherocytes form -> destroyed in spleen (extravascular hemolysis). The Coombs test detects IgG on RBC surface.

d. AIHA - Cold Type (Cold Agglutinin Disease)

Mechanism: IgM autoantibodies bind to RBC antigens (I/i antigens) at temperatures below 30°C (in peripheral circulation). IgM activates complement (C3b) on the RBC surface. When blood warms in central circulation, IgM dissociates but C3b remains. C3b-coated RBCs are phagocytosed by macrophages in the liver (liver has C3b receptors) -> extravascular hemolysis. In severe cases, full complement activation to MAC causes intravascular hemolysis.

e. Sickle Cell Disease

Mechanism: Point mutation in beta-globin gene (codon 6: glutamate -> valine) -> HbS. Under hypoxic conditions, HbS polymerizes into long fibers -> distorts the RBC into a sickle shape. Sickling is reversible initially, but repeated cycles damage the membrane -> irreversible sickled cells. Sickled cells:

Obstruct microvascular flow (vaso-occlusion) -> ischemia and infarction
Are rigid and destroyed in the spleen -> hemolysis
Repeated splenic infarction leads to autosplenectomy -> functional asplenia Polymerization is promoted by: low PO2, low pH, high 2,3-DPG, dehydration, and high HbS concentration. HbF inhibits polymerization (protective in newborns).

f. Thalassemias

Mechanism: Quantitative defect in globin chain synthesis:

Beta-thalassemia: reduced or absent beta-globin -> excess unpaired alpha chains precipitate -> oxidative membrane damage -> intramedullary destruction of erythroblasts (ineffective erythropoiesis) and peripheral hemolysis. Compensatory expansion of erythroid marrow -> skeletal deformities ("chipmunk face," "hair-on-end" skull X-ray)
Alpha-thalassemia: reduced alpha chains -> excess gamma chains form HbBart's (gamma4) or HbH (beta4) tetramers; these have very high O2 affinity and cannot deliver O2 to tissues

g. Paroxysmal Nocturnal Hemoglobinuria (PNH)

Mechanism: Acquired somatic mutation in PIG-A gene in a hematopoietic stem cell -> failure to synthesize GPI (glycosylphosphatidylinositol) anchors. GPI anchors attach complement regulatory proteins CD55 (DAF) and CD59 (MIRL) to RBC surfaces. Without these regulators, spontaneous complement activation on the RBC surface proceeds to MAC (membrane attack complex) formation -> intravascular hemolysis. Activation is greatest at night (during sleep, CO2 retention -> mild acidosis -> activates complement).

5. Aplastic Anemia

Mechanism (two main theories):

Immune-mediated (dominant theory): A drug, infection, or unknown environmental insult antigenically alters hematopoietic stem cells. Activated Th1 lymphocytes release IFN-gamma and TNF-alpha, which suppress and destroy HSCs. This explains why immunosuppression (anti-thymocyte globulin + cyclosporin) restores hematopoiesis in 60-70% of patients.
Intrinsic stem cell defect: 5-10% have mutations in telomerase (TERT/TERC genes) -> premature stem cell senescence; another 50% have abnormally short telomeres. Short telomeres may also generate neoantigens that provoke an autoimmune attack, linking both mechanisms.

6. Myelophthisic Anemia

Mechanism: Physical replacement/infiltration of the marrow by tumors (metastatic breast, lung, prostate), granulomas (TB), or storage cells -> disrupts the normal marrow architecture -> HSCs and erythroid progenitors are crowded out -> reduced production. Distortion of marrow sinusoids releases immature cells prematurely -> leukoerythroblastic picture (nucleated RBCs and immature WBCs in peripheral blood). Characteristic teardrop cells (dacryocytes) result from RBC deformation as they are squeezed through fibrotic stroma.

II. MYELOPROLIFERATIVE NEOPLASMS (MPNs)

All MPNs share the principle of constitutive (ligand-independent) activation of cytokine signaling pathways driving uncontrolled proliferation of myeloid cells.

7. Polycythemia Vera (PV)

Mechanism: >95% carry the JAK2 V617F point mutation (valine -> phenylalanine at position 617). JAK2 is a tyrosine kinase that normally transduces signals from EPO, TPO, and G-CSF receptors. V617F mutation makes JAK2 constitutively active without cytokine binding -> uncontrolled proliferation of all myeloid lineages (erythrocytes dominant). EPO levels are low because the erythroid progenitors no longer need EPO stimulation. Pruritus after hot bath results from histamine release by expanded basophil pool.

8. Essential Thrombocythemia (ET)

Mechanism: ~60% have JAK2 V617F, ~25% have CALR (calreticulin) mutations, ~5% have MPL (thrombopoietin receptor) mutations. All lead to constitutive activation of the JAK-STAT signaling pathway in megakaryocytes -> uncontrolled megakaryocyte proliferation -> massive platelet overproduction. Paradoxical bleeding occurs because very large platelet numbers absorb and deplete large vWF multimers (acquired vWD).

9. Primary Myelofibrosis (PMF)

Mechanism: Same driver mutations (JAK2, CALR, MPL) cause clonal megakaryocyte proliferation. Abnormal megakaryocytes release excessive PDGF, TGF-beta, and FGF -> stimulate marrow fibroblasts -> progressive collagen fibrosis replacing normal marrow. As the marrow fails, hematopoiesis shifts to liver and spleen (extramedullary hematopoiesis) -> massive hepatosplenomegaly. Teardrop cells form as RBCs are squeezed through fibrotic marrow.

10. Chronic Myeloid Leukemia (CML)

Mechanism: Reciprocal translocation between chromosomes 9 and 22 -> Philadelphia chromosome t(9;22)(q34;q11). The BCR gene (chr 22) fuses with the ABL1 gene (chr 9) -> BCR-ABL1 fusion oncoprotein. ABL1 normally has tightly regulated tyrosine kinase activity; BCR fusion removes this regulation -> constitutively active tyrosine kinase. BCR-ABL1 phosphorylates substrates in RAS, PI3K/AKT, and STAT5 pathways -> enhanced myeloid progenitor proliferation + inhibition of apoptosis. Disease evolves from chronic phase -> accelerated -> blast crisis as additional mutations accumulate.

III. MYELOID MALIGNANCIES

11. Acute Myeloid Leukemia (AML)

Mechanism: Two-hit model of leukemogenesis:

Class I mutations: activate proliferation/survival signaling (e.g., FLT3-ITD, RAS mutations) -> proliferative advantage
Class II mutations: block differentiation (e.g., t(8;21) RUNX1-RUNX1T1, inv(16) CBFB-MYH11, t(15;17) PML-RARA) -> immature blasts accumulate

The blasts fill the marrow, suppressing normal HSCs -> pancytopenia (anemia, thrombocytopenia, neutropenia). Special case: In AML M3 (APL), the PML-RARA fusion blocks differentiation at the promyelocyte stage; azurophilic granules in promyelocytes release procoagulants -> DIC.

12. Myelodysplastic Syndrome (MDS)

Mechanism: Clonal stem cell disorder with recurrent mutations in genes regulating:

Splicing factors (SF3B1, SRSM2, U2AF1): abnormal mRNA processing
Epigenetic regulators (TET2, DNMT3A, ASXL1, EZH2): aberrant DNA methylation and histone modification -> dysregulated gene expression
Transcription factors (RUNX1, TP53): disrupted differentiation

Result: hematopoietic progenitors undergo abnormal/dysplastic maturation and undergo excessive apoptosis within the marrow (ineffective hematopoiesis) -> cytopenias despite a hypercellular or normocellular marrow. The persistent genomic instability allows accumulation of further mutations -> transformation to AML in 30-40% of cases.

IV. LYMPHOID MALIGNANCIES

13. Acute Lymphoblastic Leukemia / Lymphoma (ALL)

Mechanism: Oncogenic mutations (chromosomal translocations, deletions, point mutations) in lymphoid progenitors block differentiation at an early stage. B-ALL often involves:

t(12;21) TEL-AML1 (most common in children, favorable prognosis)
t(9;22) BCR-ABL1 (Ph+ ALL, poor prognosis; same fusion as CML but different breakpoint -> p190 isoform)
t(1;19) E2A-PBX1
Hyperdiploidy (>50 chromosomes) = favorable

T-ALL: activating NOTCH1 mutations in >50% -> NOTCH1 normally drives T-cell differentiation; constitutive activation drives uncontrolled T-precursor proliferation.

14. Chronic Lymphocytic Leukemia (CLL)

Mechanism: Clonal expansion of mature B cells that are blocked from undergoing apoptosis. Key mechanisms:

Overexpression of BCL-2 (anti-apoptotic protein) -> cells accumulate rather than dying
Trisomy 12, deletions of 13q14 (loss of miR-15a and miR-16-1 which normally suppress BCL-2), 11q, 17p (TP53)
CLL cells receive survival signals through the B-cell receptor (BCR) signaling pathway (targeted by ibrutinib, a BTK inhibitor)
The CLL cells are immunologically incompetent -> hypogammaglobulinemia -> recurrent infections

15. Hodgkin Lymphoma (HL)

Mechanism: The neoplastic cells are Reed-Sternberg (RS) cells, derived from germinal center B cells that have lost normal B-cell gene expression. Key mechanisms:

EBV (in ~40-50%) infects B cells -> expresses LMP-1 (viral oncogene) which constitutively activates NF-kB -> promotes survival and inhibits apoptosis
EBV-negative cases: often have activating mutations in NF-kB pathway genes directly
RS cells produce cytokines (IL-5, IL-13, CCL5, CCL17) that recruit eosinophils, plasma cells, lymphocytes, and fibroblasts -> the reactive cellular background that defines each HL subtype (lymphocyte-rich, mixed cellularity, nodular sclerosis, lymphocyte-depleted)
RS cells express CD30 and CD15 (target of brentuximab vedotin)

16. Non-Hodgkin Lymphomas (NHL)

a. Diffuse Large B Cell Lymphoma (DLBCL)

Mechanism: Most arise from germinal center B cells. Key events:

BCL-6 translocations: BCL-6 is a transcriptional repressor that sustains germinal center reactions; its deregulation blocks exit from the GC state
BCL-2 translocations (in some cases via t(14;18))
MYC activation: drives proliferation
"Double-hit" (MYC + BCL-2) or "triple-hit" (MYC + BCL-2 + BCL-6) lymphomas = very aggressive due to both proliferation drive AND apoptosis resistance

b. Follicular Lymphoma

Mechanism: Hallmark translocation t(14;18)(q32;q21) juxtaposes the BCL-2 gene next to the immunoglobulin heavy chain (IgH) enhancer -> constitutive overexpression of BCL-2 protein -> blocks mitochondrial apoptosis pathway. Cells cannot die normally despite being well-differentiated. This is not sufficient alone for malignancy; secondary mutations (MYC, etc.) drive transformation to DLBCL.

c. Burkitt Lymphoma

Mechanism: Hallmark translocation t(8;14)(q24;q32) (or variants t(8;22) or t(2;8)) places the c-MYC oncogene under control of the IgH enhancer -> massive overexpression of MYC -> drives cell cycle progression, ribosome biogenesis, and metabolic reprogramming -> extremely rapid proliferation (near 100% proliferative index, Ki-67 ~100%). EBV contributes in endemic form: EBV immortalizes B cells and provides initial proliferative stimulus, allowing time for MYC translocations to occur.

d. Mantle Cell Lymphoma

Mechanism: Translocation t(11;14)(q13;q32) places cyclin D1 under the IgH enhancer -> cyclin D1 overexpression -> bypasses the G1/S cell cycle checkpoint by inactivating Rb -> uncontrolled cell cycle entry.

17. Multiple Myeloma

Mechanism: Clonal proliferation of terminally differentiated plasma cells in the bone marrow. Key molecular events:

Translocations involving IgH locus (chr 14): most commonly t(11;14) - cyclin D1; t(4;14) - MMSET/FGFR3; t(14;16) - MAF -> dysregulates proliferation
RAS and BRAF mutations: activate MAPK proliferation signaling
TP53 deletion/mutation and del(17p): loss of tumor suppression
Myeloma cells produce RANKL and suppress OPG -> osteoclast activation -> lytic bone lesions + hypercalcemia
Myeloma cells rely on the bone marrow microenvironment for survival signals (IL-6 from stromal cells -> JAK-STAT3 signaling -> key survival signal)
Monoclonal immunoglobulin (M-protein) or free light chains deposit in kidneys (cast nephropathy), nerves, and organs (AL amyloidosis)

V. BLEEDING DISORDERS

18. Hemophilia A (Factor VIII Deficiency)

Mechanism: X-linked mutation in the F8 gene -> absent or dysfunctional Factor VIII. Factor VIII is the essential cofactor for Factor IXa in the intrinsic tenase complex (IXa + VIIIa + Ca2+ + phospholipid surface). Without this complex, Factor X activation via the intrinsic pathway is severely impaired. The extrinsic pathway (TF + VIIa) can activate some Factor X and generate a small initial thrombin burst, but insufficient thrombin is generated to sustain a stable clot -> bleeding after injury, particularly into joints (hemarthrosis) and deep tissues.

19. Hemophilia B (Factor IX Deficiency)

Mechanism: X-linked mutation in the F9 gene -> absent or dysfunctional Factor IX. Factor IX is the serine protease activated by both the intrinsic pathway (XIa) and the extrinsic pathway (TF-VIIa complex). Without IXa, the tenase complex cannot form -> same downstream failure as Hemophilia A (insufficient Factor X activation via intrinsic pathway). Clinically identical to Hemophilia A.

20. Von Willebrand Disease (vWD)

Mechanism: Deficiency or dysfunction of von Willebrand Factor (vWF):

vWF normally binds GPIb on platelets AND subendothelial collagen -> acts as a bridge anchoring platelets to damaged vessel walls (primary hemostasis)
vWF also carries and protects Factor VIII from proteolytic degradation in circulation
In vWD: impaired platelet adhesion -> deficient platelet plug formation -> mucocutaneous bleeding (nosebleeds, menorrhagia, GI bleeding)
Type 1: quantitative partial reduction; Type 2: qualitative defect; Type 3: complete absence

21. Immune Thrombocytopenic Purpura (ITP)

Mechanism: Autoimmune production of IgG antibodies targeting platelet surface glycoproteins - most commonly GPIIb/IIIa (integrin αIIbβ3) or GPIb/IX complex. IgG-coated platelets are recognized by Fc-gamma receptors on macrophages in the spleen -> phagocytosis and destruction. The spleen is also the primary site of autoantibody production. Additionally, cytotoxic T lymphocytes directly destroy platelets. Megakaryopoiesis is also suppressed by anti-GPIIb/IIIa antibodies cross-reacting with megakaryocyte surface.

22. Thrombotic Thrombocytopenic Purpura (TTP)

Mechanism: Deficiency or inhibition of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs 13), the protease that cleaves ultra-large vWF (ULvWF) multimers secreted by endothelial cells. Without ADAMTS13, ULvWF multimers accumulate on endothelial surfaces -> spontaneously bind and activate platelets -> platelet microthrombi in terminal arterioles and capillaries throughout multiple organs -> thrombocytopenia (consumption), MAHA (RBCs sheared by fibrin strands = schistocytes), and ischemic organ damage (brain, kidneys).

Acquired TTP: autoantibodies against ADAMTS13
Congenital (Upshaw-Schulman syndrome): ADAMTS13 gene mutations

23. Disseminated Intravascular Coagulation (DIC)

Mechanism: Pathological systemic activation of coagulation triggered by:

Endotoxin (sepsis) and cytokines (TNF, IL-1) -> upregulate tissue factor (TF) expression on monocytes and endothelium -> massive TF-VIIa driven thrombin generation throughout the circulation
Obstetric emergencies (amniotic fluid embolism): amniotic fluid is rich in TF and phospholipids -> direct activation
AML M3 / malignancy: granule contents of promyelocytes contain TF-like substances; some cancers express TF constitutively
Consequence: widespread microvascular thrombosis (ischemia) simultaneously with consumption of clotting factors and platelets -> paradoxical bleeding. Plasminogen is also activated -> fibrinolysis -> fibrin degradation products (D-dimer) accumulate, which themselves inhibit platelet function and fibrin polymerization.

24. Heparin-Induced Thrombocytopenia (HIT)

Mechanism: Heparin binds platelet factor 4 (PF4), a protein released from platelet alpha granules. The heparin-PF4 complex is recognized as foreign -> IgG antibodies form against the complex. These antibodies bind to heparin-PF4 on platelet surfaces -> cross-link platelet FcγRIIa receptors -> platelet activation -> platelet aggregation and consumption (thrombocytopenia) AND paradoxical thrombosis (not bleeding). This makes HIT a pro-thrombotic, not a hemorrhagic, disorder.

VI. OTHER IMPORTANT DISORDERS

25. Polycythemia (Secondary)

Mechanism: Physiologic: chronic hypoxia (COPD, high altitude, sleep apnea, cyanotic heart disease) activates HIF-1alpha (hypoxia-inducible factor) in the kidney -> transcription of EPO gene -> excess EPO stimulates erythropoiesis. Pathologic: EPO-secreting tumors (renal cell carcinoma, hepatocellular carcinoma, cerebellar hemangioblastoma) produce EPO autonomously regardless of oxygen levels.

26. Hemolytic Uremic Syndrome (HUS)

Mechanism: Most commonly caused by Shiga toxin-producing E. coli (STEC, O157:H7). Shiga toxin binds GB3 receptors on renal endothelial cells and glomerular cells -> internalized -> inhibits protein synthesis -> endothelial cell death -> subendothelial damage exposes collagen + triggers platelet aggregation + activates complement -> microvascular thrombosis predominantly in renal microvasculature -> microangiopathic hemolytic anemia + thrombocytopenia + acute kidney injury (the triad of HUS). Overlaps with TTP but is primarily renal and does not involve ADAMTS13 deficiency.

27. Myelodysplastic/Myeloproliferative Overlap Neoplasms (e.g., CMML)

Mechanism: Chronic myelomonocytic leukemia (CMML) arises from mutations in both proliferation pathways (RAS family mutations in ~30%) and epigenetic/splicing regulators (TET2, SRSF2) -> both dysplastic features (ineffective hematopoiesis, cytopenias) AND proliferative features (monocytosis, splenomegaly) coexist.

28. Lymphocytosis / Reactive Changes

Mechanism: Infectious mononucleosis (EBV): EBV infects B cells via CD21 (complement receptor 2) -> viral gene products (LMP-1, LMP-2, EBNA) activate B cells and drive proliferation -> massive reactive T-cell response (the "atypical lymphocytes" = activated CD8+ cytotoxic T cells attempting to control EBV-infected B cells). This explains lymphadenopathy, splenomegaly, and pharyngitis.

Quick Reference: Core Molecular Mechanisms

Disorder	Core Molecular Lesion
Iron deficiency anemia	Hepcidin/ferroportin axis -> iron unavailable for heme synthesis
ACD	IL-6 -> hepcidin -> iron trapping in macrophages
Megaloblastic anemia	Defective thymidylate synthesis -> impaired DNA replication
PNH	PIG-A mutation -> loss of CD55/CD59 -> uncontrolled complement
Aplastic anemia	T-cell mediated destruction of HSCs + telomerase defects
Sickle cell	HbS polymerization under hypoxia -> vaso-occlusion + hemolysis
PV	JAK2 V617F -> constitutive cytokine-independent signaling
CML	BCR-ABL1 -> constitutive tyrosine kinase -> uncontrolled myelopoiesis
AML	Class I (proliferation) + Class II (differentiation block) mutations
MDS	Splicing/epigenetic mutations -> ineffective hematopoiesis + apoptosis
CLL	BCL-2 overexpression + BCR signaling -> apoptosis resistance
Follicular lymphoma	t(14;18) -> BCL-2 overexpression -> blocked apoptosis
Burkitt lymphoma	t(8;14) -> MYC overexpression -> explosive proliferation
Hodgkin lymphoma	NF-kB activation (EBV/LMP-1 or direct mutation) -> RS cell survival
Multiple myeloma	IgH translocations + IL-6/JAK-STAT3 survival + RANK/RANKL bone destruction
Hemophilia A	No Factor VIII -> intrinsic tenase complex fails -> insufficient thrombin
vWD	No vWF bridge -> platelet adhesion fails -> mucocutaneous bleeding
ITP	Anti-GPIIb/IIIa IgG -> splenic phagocytosis of platelets
TTP	ADAMTS13 deficiency -> ULvWF accumulation -> platelet microthrombi
DIC	Systemic TF activation -> coagulation factor consumption + microvascular thrombi
HIT	Anti-PF4/heparin IgG -> platelet Fc receptor activation -> thrombosis

Sources: Robbins, Cotran & Kumar Pathologic Basis of Disease | Robbins & Kumar Basic Pathology | Harrison's Principles of Internal Medicine 22E | Henry's Clinical Diagnosis and Management by Laboratory Methods

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