Clinical Volume Pearls
30% acute loss: hypovolemic shock
Hemodilution (massive crystalloids / sepsis): protein drop → edema / drug binding changes |
Marrow / Stem-Cell Disorders
Aplastic Anemia |
Myelodysplastic Syndromes |
Leukemias |
Myelofibrosis |
Polycythemia Vera / Essential Thrombocythemia / CML |
hypocellular marrow (immune/drug/toxin) → pancytopenia, low retic, empty biopsy |
cellular marrow with dysplasia & ineffective hematopoiesis → cytopenias, macrocytic indices, risk of AML |
malignant blast proliferation (> 20% blasts in marrow) → anemia, infections, bleeding |
collagen deposition in marrow, JAK2/CALR/MPL mutations → EMH, massive spleen, teardrops |
myeloproliferative neoplasms with overproduction of mature myeloid elements |
Hypercoagulability
↑ platelet function → endothelial injury (atherosclerosis, DM, smoking, hyperlipidemia)
↑ clotting activity
- inherited: factor V leiden (APC resistance), prothrombin G20210A, protein C/S or ATIII deficiency
- acquired: pregnancy/OCPs, stasis (immobility, CHF), malignancy, antiphospholipid syndrome, inflammation/sepsis |
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Plasma Proteins
Albumin (54%) |
Globulins (38%) |
Fibrinogen (7%) |
large, stays intravascular: maintains colloid oncotic pressure |
α-globulins → bilirubin & steroids |
soluble: thrombin converts to insoluble fibrin → coagulation mesh |
carrier for bilirubin, hormones, FFAs, many drugs |
β-globulins → iron (transferrin) & copper (ceruloplasmin) |
when removed, remaining fluid = serum |
↓ albumin (cirrhosis, nephrotic syndrome, malnutrition) → edema, ↑ free drug fraction |
γ-globulins → immunoglobulins (antibodies) |
Lab distinction: order plasma for coagulation studies (contains fibrinogen) vs serum for chemistries / antibodies
Diagnostic Cornerstones
CBC & Differential |
Reticulocyte Count / Index |
ESR |
Bone-Marrow Aspiration (cell morphology, iron stores, blast %), Core Biopsy (cellularity, fibrosis, architecture) |
Peripheral Smear Clues |
Hb |
distinguishes underproduction vs peripheral loss hemolysis/bleed |
height RBC falls in 1 hr |
posterior iliac crest standard |
schistocytes (MAHA/DIC |
Hct |
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trend in RA, temporal arteritis, SLE |
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spherocytes (auto-immune hemolysis) |
MCV (micro- vs macrocytic) |
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teardrops (myelofibrosis/EMH) |
MCHC |
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blasts (leukemia) |
RDW |
WBC absolute counts |
platelets & MPV |
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Hematopoiesis
Developmental migration → yolk sac (wk 2-8) → liver + spleen (wk 8-7 mo gestation) → bone marrow (≧7 mo fetal & post-natal)
Adult active (red) marrow restricted to axial skeleton & proximal long bones: yellow marrow = fat (can reconvert under stress)
Pluripotent hematopoietic stem cell (HSC): self-renewing: differentiates to:
- Common myeloid progenitor → CFU-E (erythroid), CFU-GM (granulocyte/monocyte), CFU-Meg (megakaryocyte)
- Common lymphoid progenitor → pro-B, pro-T, NK
Cytokine / growth-factor regulation:
- Erythropoietin (EPO) — renal peritubular cells respond to hypoxia → ↑ RBC proliferation & Hb synthesis
- Granulocyte-CSF / GM-CSF — drive neutrophil & monocyte lines: pharmacologic G-CSF (filgrastim) for chemo induced neutropenia
- Thrombopoietin (TPO) — hepatic & renal origin: binds megakaryocytes & platelets → controls platelet mass
- IL-3, IL-5, IL-7 fine-tune lineage commitment
Extramedullary hematopoiesis (EMH):
- Occurs when marrow incapable (fibrosis, infiltration, hemolytic stress) → liver & spleen resume fetal role → splenomegaly, leuko-erythroblastic smear, tear-drop RBCs |
Normal Hemostatic Sequence
1. Vascular Spasm |
2. Platelet Activation |
3. Platelet Activation + Aggregation |
4. Coagulation Cascade |
5. Clot Retraction & Fibrinolysis |
endothelin-1 (endothelium), thromboxane A2 & serotonin (platelets) ↓ blood flow |
vWF binds exposed collagen, links to platelet GP Ib |
shape change: dense-granule release (ADP, Ca2+, serotonin): GP IIb/IIIa binds fibrinogen → primary plug |
intrinsic (contact): XII → XI → IX (+VIII) → Xa |
platelet actin-myosin contracts: tPA converts plasminogen → plasmin: plasmin degrades fibrin → D-dimers |
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extrinsic (tissue factor): TF + VIIa → Xa (fast) |
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common: Xa + Va + Ca2+ + phospholipid → prothrombin → thrombin: thrombin converts fibrinogen → fibrin, activates V, VIII, XIII and platelets |
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anticoagulant safeguards: ATIII (heparin-cofactor), protein C/S, TFPI |
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