30 types blood and body fluid system disease treatment investigation finding differential diagnosis contraindications ICU and OPD and blood transfusion and type of anemia diagnosis summary

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Here is a comprehensive clinical reference for 30 Blood & Body Fluid System Diseases covering treatment, investigations, findings, differential diagnosis, contraindications, ICU/OPD management, blood transfusion, and types of anemia.

🩸 30 BLOOD & BODY FLUID SYSTEM DISEASES — COMPLETE CLINICAL REFERENCE

SECTION A: TYPES OF ANEMIA (Overview)

Type	MCV	Key Feature
Iron deficiency	Low (microcytic)	↓Ferritin, ↑TIBC
Thalassemia	Low (microcytic)	Normal/↑ferritin, Hb electrophoresis abnormal
Sideroblastic	Low/normal	Ring sideroblasts on BM biopsy
B12/Folate deficiency	High (macrocytic)	Hypersegmented neutrophils
Aplastic anemia	Normal/high	Pancytopenia, hypocellular BM
Hemolytic anemia	Normal	↑LDH, ↑bilirubin, ↓haptoglobin
Anemia of chronic disease	Low/normal	↑ferritin, ↓TIBC
Pernicious anemia	High	Anti-intrinsic factor antibodies

1. 🔴 IRON DEFICIENCY ANEMIA (IDA)

Summary: Most common anemia worldwide. Caused by blood loss, poor intake, malabsorption, or increased demand (pregnancy).

Investigations:

CBC: ↓Hb, ↓MCV, ↓MCH, microcytic hypochromic picture
Serum ferritin ↓ (most sensitive), ↓serum iron, ↑TIBC
Blood film: pencil cells, target cells, anisocytosis
Reticulocyte count: low
Bone marrow (rarely needed): absent iron stores

Findings: Pallor, koilonychia (spoon nails), angular stomatitis, glossitis, pica, Plummer-Vinson syndrome (dysphagia + IDA)

Differential Diagnosis: Thalassemia trait, anemia of chronic disease, sideroblastic anemia

Treatment:

Ferrous sulfate 200 mg TDS orally for 3–6 months (continue 3 months after Hb normalizes)
IV iron (ferric carboxymaltose) if oral intolerance, malabsorption, or IBD
Treat underlying cause (GI bleed, menorrhagia)

Blood Transfusion: Only if Hb <7 g/dL symptomatic, or <8 g/dL with cardiac disease; transfuse 1 unit packed RBC and recheck

Contraindications: IV iron contraindicated in active infection; iron tablets worsen constipation — avoid in bowel obstruction

OPD: Iron tablets + dietary advice (red meat, leafy greens); follow-up CBC at 4–6 weeks ICU: IV iron infusion preferred; transfuse if hemodynamically compromised; Hb target ≥8 g/dL in ICU

2. 🔴 VITAMIN B12 DEFICIENCY (MEGALOBLASTIC ANEMIA)

Summary: Deficiency of cobalamin → impaired DNA synthesis → megaloblastic anemia + neurological damage.

Investigations:

CBC: macrocytic anemia (MCV >100 fL), pancytopenia in severe cases
Blood film: hypersegmented neutrophils (≥5 lobes), macro-ovalocytes
↓Serum B12, ↑methylmalonic acid, ↑homocysteine
Anti-intrinsic factor antibodies (pernicious anemia)
Schilling test (historical)

Findings: Pallor, glossitis, peripheral neuropathy (subacute combined degeneration of spinal cord), dementia, lemon-yellow skin

Differential Diagnosis: Folate deficiency, liver disease, hypothyroidism, drug-induced (methotrexate, hydroxyurea)

Treatment:

Hydroxocobalamin 1 mg IM every other day × 2 weeks, then 1 mg IM every 3 months (lifelong in pernicious anemia)
Or oral B12 1000 mcg/day if dietary cause

Blood Transfusion: Rarely needed; only if severe symptomatic anemia (Hb <7)

Contraindications: B12 replacement should precede folate in combined deficiency (folate alone worsens neurological damage from B12 deficiency)

OPD: Monitor B12 levels, neurological assessment, dietary counseling ICU: IV B12 if unable to take IM; monitor potassium (hypokalemia risk during treatment — "hungry bone" equivalent)

3. 🔴 FOLATE DEFICIENCY ANEMIA

Summary: Dietary deficiency (alcoholics, elderly, pregnancy), malabsorption, drugs (methotrexate, phenytoin).

Investigations:

CBC: macrocytic anemia
↓Serum folate, ↓RBC folate
↑Homocysteine (but NOT methylmalonic acid — distinguishes from B12 deficiency)
Blood film: hypersegmented neutrophils

Findings: Pallor, glossitis, stomatitis — no neurological features (unlike B12)

Differential Diagnosis: B12 deficiency, liver disease, drug-induced macrocytosis

Treatment: Folic acid 5 mg PO daily × 4 months; dietary correction

Contraindications: Do not give folic acid without B12 replacement if B12 deficiency is also present

OPD: Supplement in pregnancy (5 mg/day) to prevent neural tube defects ICU: Rarely ICU-level; supplement IV if severe

4. 🟠 APLASTIC ANEMIA

Summary: Immune destruction or depletion of hematopoietic stem cells → pancytopenia + hypocellular bone marrow.

Investigations:

CBC: pancytopenia (↓Hb, ↓WBC, ↓platelets)
Reticulocyte count: very low
Bone marrow biopsy: hypocellular/fatty marrow (diagnostic)
Ham test/flow cytometry (to exclude PNH)
LFTs, viral screen (EBV, CMV, hepatitis), chromosomes

Findings: Pallor, bleeding (petechiae, purpura), infections, no splenomegaly

Differential Diagnosis: PNH, hypoplastic MDS, B12/folate deficiency, leukemia

Severity:

Severe: BM cellularity <25%, 2 of: neutrophils <0.5×10⁹/L, platelets <20×10⁹/L, reticulocytes <20×10⁹/L
Very severe: neutrophils <0.2×10⁹/L

Treatment:

Young patient + donor available: Allogenic bone marrow transplant (treatment of choice in severe)
No donor: Anti-thymocyte globulin (ATG) + cyclosporine + eltrombopag
Supportive: transfusions, G-CSF, antibiotics, antifungals

Blood Transfusion: Use irradiated, CMV-negative blood; minimize transfusions pre-transplant to reduce allosensitization

Contraindications: Avoid live vaccines; avoid NSAIDs (↑bleeding risk)

OPD: Monitor CBC, cyclosporine levels, infection surveillance ICU: Protective isolation, broad-spectrum antibiotics for neutropenic sepsis, transfusion support

5. 🟠 HEMOLYTIC ANEMIA

Summary: Premature destruction of RBCs — intrinsic (hereditary spherocytosis, G6PD, sickle cell) or extrinsic (autoimmune, TTP, malaria).

Investigations:

CBC: normocytic anemia, ↑reticulocyte count
Blood film: spherocytes/schistocytes/sickle cells depending on cause
↑LDH, ↑indirect bilirubin, ↓haptoglobin
Direct Coombs test (positive in autoimmune)
Osmotic fragility (hereditary spherocytosis), G6PD assay, Hb electrophoresis

Findings: Pallor, jaundice, splenomegaly, dark urine (hemoglobinuria in intravascular)

Differential Diagnosis: Liver disease, Gilbert syndrome, ineffective erythropoiesis

Treatment:

Autoimmune (AIHA): Prednisolone 1 mg/kg/day → rituximab → splenectomy
G6PD deficiency: avoid triggers (fava beans, oxidant drugs, infections)
Hereditary spherocytosis: splenectomy
Cold AIHA: avoid cold, chlorambucil

Blood Transfusion: Difficult due to antibodies; use least incompatible unit; consult transfusion medicine

Contraindications: Blood transfusion in cold AIHA — warm blood; avoid oxidant drugs in G6PD deficiency

OPD: Folate supplementation, avoid triggers, vaccination post-splenectomy ICU: Severe hemolytic crisis — transfuse cautiously, plasma exchange in TTP

6. 🟡 SICKLE CELL DISEASE (SCD)

Summary: Autosomal recessive; point mutation in β-globin gene (HbS). Sickling in hypoxia → vaso-occlusion, hemolysis, organ damage.

Investigations:

Hb electrophoresis (HbSS, HbSC, HbS-β-thal)
CBC: chronic normocytic anemia, Hb 6–9 g/dL
Blood film: sickle cells, target cells, Howell-Jolly bodies
Reticulocyte count: elevated
Sickle solubility test

Findings: Painful crises (bone, abdomen), acute chest syndrome, stroke, splenic sequestration, priapism, leg ulcers, avascular necrosis of femoral head, chronic renal disease, proliferative retinopathy

Differential Diagnosis: Other hemoglobinopathies, acute abdomen, osteomyelitis

Treatment:

Hydroxyurea (increases HbF, reduces crises)
Voxelotor, crizanlizumab (newer agents)
Allogeneic BMT (potentially curative)
Gene therapy (emerging)
Supportive: analgesia (paracetamol → NSAIDs → opioids), hydration, O₂, folate

Blood Transfusion:

Simple transfusion (acute symptomatic anemia, pre-op)
Exchange transfusion (acute chest syndrome, stroke, priapism, pre-op major surgery) — target HbS <30%

Contraindications: Avoid dehydration, hypoxia, cold, acidosis (triggers sickling); avoid high-dose transfusion without exchange (hyperviscosity)

OPD: Prophylactic penicillin (lifelong — functional asplenia), pneumococcal/meningococcal/Hib vaccines, hydroxyurea, ophthalmology, nephrology follow-up ICU: Acute chest syndrome — O₂, exchange transfusion, antibiotics (covers atypicals), incentive spirometry; Stroke — emergency exchange transfusion

7. 🟡 THALASSEMIA

Summary: Reduced synthesis of α or β globin chains → ineffective erythropoiesis, hemolysis, iron overload.

Investigations:

CBC: microcytic hypochromic anemia (very low MCV, Hb variable)
Hb electrophoresis: ↑HbA₂ (β-thal trait), absent HbA (β-thal major)
Blood film: target cells, microcytes, nucleated RBCs
Serum ferritin: elevated
Genetic testing

Findings: β-thal major: severe anemia from infancy, jaundice, hepatosplenomegaly, "chipmunk face" (maxillary prominence), "hair-on-end" skull X-ray, growth retardation

Differential Diagnosis: IDA, sickle cell disease, other hemoglobinopathies

Treatment:

β-thal major: Regular transfusions (every 3–4 weeks, target Hb >10 g/dL) + iron chelation (desferrioxamine, deferasirox)
Curative: Allogeneic BMT, gene therapy (betibeglogene — approved)
β-thal trait: No treatment needed

Blood Transfusion: Leukodepleted, extended matched pRBC; regular transfusion program

Contraindications: Avoid iron supplements in thalassemia (already iron overloaded); avoid unmatched blood (alloimmunization risk)

OPD: Iron chelation monitoring, cardiac MRI (iron deposition), endocrine surveillance (DM, hypothyroidism) ICU: Acute splenic sequestration, cardiac failure from iron overload

8. 🟡 GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY

Summary: X-linked; most common RBC enzyme defect; hemolysis triggered by oxidative stress.

Investigations: G6PD enzyme assay (sample after hemolytic crisis resolves), blood film during crisis (bite cells, Heinz bodies on supravital stain), ↑bilirubin, ↓haptoglobin

Findings: Episodic hemolysis (jaundice, dark urine) triggered by fava beans, infections, drugs (dapsone, primaquine, nitrofurantoin, rasburicase)

Differential Diagnosis: Other hemolytic anemias, hepatitis

Treatment: Remove trigger, supportive care, transfusion if severe; neonatal jaundice → phototherapy/exchange transfusion

Contraindications: Avoid primaquine, dapsone, rasburicase, nitrofurantoin, high-dose aspirin, methylene blue in G6PD deficiency

OPD: Patient education on triggers; carry medic alert card ICU: Rare; severe hemolysis may require transfusion support

9. 🟡 HEREDITARY SPHEROCYTOSIS

Summary: Autosomal dominant; spectrin/ankyrin defect → spherical rigid RBCs → splenic destruction.

Investigations: Blood film: spherocytes, ↑MCHC; osmotic fragility test ↑; EMA binding test (flow cytometry); DAT negative

Findings: Hemolytic anemia, jaundice, splenomegaly, gallstones (pigment), aplastic crises (parvovirus B19)

Differential Diagnosis: AIHA (DAT positive vs. negative), ABO incompatibility

Treatment: Folate supplementation; splenectomy (definitive in moderate-severe) — post-splenectomy vaccines; cholecystectomy if gallstones

Blood Transfusion: Parvovirus-induced aplastic crisis — transfusion support

OPD: Monitor Hb, surveillance for gallstones; delay splenectomy until age >6 years ICU: Aplastic crisis or severe hemolysis

10. 🟠 PERNICIOUS ANEMIA

Summary: Autoimmune atrophic gastritis → loss of intrinsic factor → vitamin B12 malabsorption.

Investigations: ↓B12, macrocytic anemia, anti-intrinsic factor antibodies (specific), anti-parietal cell antibodies, ↑gastrin, endoscopy showing atrophic gastritis

Findings: Pallor, glossitis, subacute combined degeneration (posterior/lateral columns), dementia, lemon-yellow tinge, increased gastric cancer risk

Treatment: Hydroxocobalamin IM lifelong; monitor for gastric cancer

OPD: Annual CBC, B12 levels, screen for associated autoimmune diseases (thyroid, T1DM, vitiligo) Contraindications: Oral B12 ineffective in pernicious anemia (no intrinsic factor)

11. 🔵 ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Summary: Malignant proliferation of lymphoblasts; most common childhood cancer.

Investigations: CBC: ↑WBC (lymphoblasts), anemia, thrombocytopenia; Blood film: lymphoblasts; Bone marrow biopsy: >20% blasts; Immunophenotyping (B-ALL vs T-ALL); Cytogenetics (Philadelphia chromosome — t(9;22) — poor prognosis); CSF analysis (CNS involvement)

Findings: Pallor, bleeding, infections, lymphadenopathy, hepatosplenomegaly, mediastinal mass (T-ALL), CNS disease (headache, cranial nerve palsy)

Differential Diagnosis: AML, CLL, lymphoma, infectious mononucleosis, aplastic anemia

Treatment:

Induction: vincristine + dexamethasone + asparaginase ± anthracycline
Consolidation, maintenance (2–3 years)
CNS prophylaxis: intrathecal methotrexate
Ph+ ALL: add imatinib/dasatinib
Relapse/refractory: CAR-T cell therapy (tisagenlecleucel), blinatumomab, allogeneic BMT

Contraindications: Live vaccines contraindicated during chemotherapy; avoid NSAIDs (thrombocytopenia)

Blood Transfusion: pRBC if Hb <7–8; platelets if <10×10⁹/L or bleeding; use irradiated products

OPD: Chemotherapy protocols, infection prophylaxis (cotrimoxazole for PCP), antifungal prophylaxis ICU: Febrile neutropenia — empiric broad-spectrum antibiotics; tumor lysis syndrome — IV fluids, allopurinol/rasburicase, electrolyte monitoring

12. 🔵 ACUTE MYELOID LEUKEMIA (AML)

Summary: Clonal malignancy of myeloid precursors; most common acute leukemia in adults.

Investigations: CBC: ↑WBC or low/normal with blasts; Bone marrow: ≥20% myeloblasts; Auer rods on blood film (pathognomonic); Flow cytometry; Cytogenetics (t(15;17) = APL — good prognosis; complex karyotype — poor); Molecular: FLT3, NPM1, IDH1/2 mutations

Findings: Fatigue, infections, bleeding (DIC especially in APL/M3), gum hypertrophy (M4/M5), skin infiltration

Differential Diagnosis: ALL, MDS, aplastic anemia, CML blast crisis

Treatment:

Standard: "7+3" induction (cytarabine × 7 days + daunorubicin × 3 days)
APL (M3): ATRA + arsenic trioxide (ATO) — highly effective
Targeted: midostaurin (FLT3+), venetoclax + azacitidine (older/unfit patients), IDH inhibitors
Consolidation + allogeneic BMT in high-risk

Blood Transfusion: pRBC, platelets, FFP/cryoprecipitate (especially DIC in APL); irradiated products

Contraindications: Anthracyclines contraindicated in severe cardiac dysfunction; arsenic QTc prolongation monitoring

OPD: CBC monitoring, bone marrow assessment for remission ICU: DIC, leukostasis (hyperleukocytosis — leukapheresis), febrile neutropenia, tumor lysis syndrome

13. 🔵 CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Summary: Clonal accumulation of mature but functionally incompetent B lymphocytes; most common adult leukemia in the West.

Investigations: CBC: ↑lymphocytes (>5×10⁹/L); Blood film: small mature lymphocytes + smudge cells; Immunophenotyping (CD5+, CD19+, CD23+, dim surface Ig); CT scan; IGHV mutation status, del(17p), del(11q) — for prognosis

Findings: Often asymptomatic (found on routine CBC); lymphadenopathy, splenomegaly, recurrent infections, autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP)

Staging:

Rai: 0 (lymphocytosis only) → IV (thrombocytopenia)
Binet: A → C

Differential Diagnosis: Other lymphomas, ALL, hairy cell leukemia, reactive lymphocytosis

Treatment:

Early stage/asymptomatic: "Watch and wait"
Symptomatic/progressive: Ibrutinib (BTK inhibitor), venetoclax + obinutuzumab
Previous standard: FCR (fludarabine + cyclophosphamide + rituximab)
Allogeneic BMT for high-risk

Contraindications: Live vaccines contraindicated; ibrutinib — caution with anticoagulants (bleeding risk), avoid with strong CYP3A4 inhibitors

Blood Transfusion: For AIHA — careful cross-match; use washed or irradiated blood

OPD: Infection prophylaxis (immunoglobulin replacement if recurrent infections), monitor CBC/LN ICU: Rarely needed unless Richter's transformation (to DLBCL), severe autoimmune complications

14. 🔵 CHRONIC MYELOID LEUKEMIA (CML)

Summary: BCR-ABL1 fusion gene (Philadelphia chromosome t(9;22)) → unregulated tyrosine kinase → myeloid expansion.

Investigations: CBC: ↑WBC (10–500×10⁹/L), full spectrum of myeloid cells; Blood film: myelocytes, basophilia, eosinophilia; BM biopsy; PCR for BCR-ABL1 (diagnosis and monitoring); FISH; NAP score: low (distinguishes from reactive leukocytosis)

Findings: Fatigue, night sweats, weight loss, massive splenomegaly, left upper quadrant pain

Differential Diagnosis: Leukemoid reaction (NAP score high), other myeloproliferative neoplasms

Phases: Chronic → Accelerated → Blast crisis

Treatment:

First-line: Imatinib (TKI) 400 mg PO daily; or dasatinib/nilotinib (2nd-gen, faster response)
Monitor BCR-ABL1 by PCR (molecular response)
Blast crisis: treat like AML/ALL + TKI; consider allogeneic BMT

Contraindications: Imatinib — hepatotoxicity (monitor LFTs); avoid in pregnancy (teratogenic); dasatinib — pleural effusion risk

OPD: Monthly CBC initially, BCR-ABL PCR every 3 months ICU: Leukostasis (extreme leukocytosis → leukapheresis), blast crisis

15. 🟣 MULTIPLE MYELOMA

Summary: Malignant plasma cell proliferation → paraprotein (M-protein), bone destruction, renal failure, hypercalcemia, immunosuppression.

CRAB Criteria (end-organ damage): Calcium ↑, Renal failure, Anemia, Bone lesions

Investigations:

SPEP/UPEP: monoclonal protein (M-band); serum free light chains
Bone marrow biopsy: ≥10% plasma cells (clonal)
X-ray/PET/MRI: lytic lesions ("punched out"), vertebral fractures
CBC: normocytic anemia, ↑ESR, rouleaux formation
Serum calcium ↑, creatinine ↑, β2-microglobulin (staging), LDH
Urine: Bence-Jones protein

Findings: Bone pain (back/ribs), pathological fractures, hypercalcemia (polyuria, constipation, confusion), recurrent infections, renal failure, peripheral neuropathy, amyloidosis

Differential Diagnosis: MGUS, lymphoma, metastatic carcinoma, Waldenström's macroglobulinemia

Treatment:

Transplant-eligible: VRd (bortezomib + lenalidomide + dexamethasone) induction → autologous SCT → lenalidomide maintenance
Transplant-ineligible: VRd or VMP (bortezomib + melphalan + prednisone)
Relapsed: daratumumab-based regimens, carfilzomib, pomalidomide
Supportive: bisphosphonates (zoledronic acid), EPO, IVIG, vertebroplasty

Blood Transfusion: pRBC for symptomatic anemia; EPO may reduce transfusion need

Contraindications: Bortezomib — peripheral neuropathy (monitor); thalidomide/lenalidomide — VTE prophylaxis mandatory (use LMWH/aspirin); avoid bisphosphonates if eGFR <30 (zoledronic acid)

OPD: Bisphosphonates monthly IV; M-protein monitoring; bone protection; infection prophylaxis (acyclovir, cotrimoxazole) ICU: Hypercalcemic crisis (IV fluids + zoledronic acid + calcitonin), AKI from light chain cast nephropathy (dialysis if severe), hyperviscosity syndrome (plasmapheresis)

16. 🟣 NON-HODGKIN LYMPHOMA (NHL)

Summary: Heterogeneous group of B- and T-cell lymphoid malignancies; DLBCL (most common aggressive) and follicular lymphoma (most common indolent).

Investigations: Excisional lymph node biopsy (mandatory); immunohistochemistry; CT PET staging; CBC (cytopenias if BM involved); LDH (prognosis), β2-microglobulin; BM biopsy; BCL2, BCL6, MYC rearrangements

Findings: Painless lymphadenopathy, B symptoms (fever >38°C, night sweats, weight loss >10%), hepatosplenomegaly, extranodal disease (GI, CNS, skin)

Differential Diagnosis: Hodgkin lymphoma, reactive lymphadenopathy, CLL, metastatic carcinoma

Treatment:

DLBCL: R-CHOP (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisolone)
Follicular lymphoma: watch-and-wait or rituximab ± chemotherapy; obinutuzumab
Relapsed/refractory: R-ICE/R-DHAP → autologous SCT; CAR-T (axicabtagene ciloleucel)
CNS lymphoma: high-dose methotrexate

Blood Transfusion: pRBC/platelets for BM involvement

Contraindications: Anthracyclines (doxorubicin) — avoid LVEF <50%; rituximab — reactivation of HBV (screen all patients, give prophylactic antiviral)

OPD: Tumor lysis prophylaxis, infection prophylaxis, follow-up imaging ICU: Tumor lysis syndrome, superior vena cava obstruction, ureteric obstruction, CNS compression

17. 🟣 HODGKIN LYMPHOMA

Summary: Reed-Sternberg cells on biopsy (CD15+, CD30+); bimodal age distribution (young adults + elderly); excellent prognosis.

Investigations: Excisional biopsy (RS cells); CT/PET staging (Ann Arbor); CBC, ESR, albumin, LDH; BM biopsy

Findings: Painless rubbery cervical lymphadenopathy, B symptoms, mediastinal mass, Pel-Ebstein fever, alcohol-induced pain in lymph nodes (classic)

Staging: Ann Arbor I–IV; IPS (International Prognostic Score)

Treatment:

Early/favorable: ABVD × 2 cycles + radiation
Advanced: ABVD × 6 cycles or BEACOPP
Relapsed: salvage chemotherapy → autologous SCT; brentuximab vedotin (anti-CD30); pembrolizumab/nivolumab (PD-1 inhibitors)

Contraindications: Bleomycin — pulmonary toxicity (monitor PFTs); avoid bleomycin in advanced age or lung disease; ABVD — cumulative cardiotoxicity

OPD: Surveillance imaging, long-term toxicity monitoring (hypothyroidism, secondary malignancies, cardiac, pulmonary) ICU: SVC syndrome, massive mediastinal disease causing airway compromise

18. 🟤 DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Summary: Widespread pathological activation of coagulation → microvascular thrombosis + consumption of clotting factors/platelets → bleeding.

Causes: Sepsis (most common), trauma, obstetric complications (abruption, amniotic fluid embolism), malignancy (especially APL), snake bite, massive transfusion

Investigations:

↑PT, ↑APTT, ↓fibrinogen (<1.5 g/L), ↓platelets
↑D-dimer (very sensitive), ↑FDPs
Blood film: schistocytes (microangiopathic hemolysis)
ISTH DIC score

Findings: Oozing from IV sites, petechiae, purpura, organ failure, acral cyanosis, bleeding from multiple sites + simultaneous thrombosis

Differential Diagnosis: TTP, HUS, HIT, severe liver disease, primary fibrinolysis

Treatment:

Treat underlying cause (paramount)
FFP: if bleeding + ↑PT/APTT (replace clotting factors)
Cryoprecipitate: if fibrinogen <1.5 g/L (replaces fibrinogen, Factor VIII, vWF)
Platelets: if <50×10⁹/L with active bleeding or <20×10⁹/L without
Heparin: only if predominant thrombosis (purpura fulminans, acral ischemia)
Tranexamic acid: generally avoided (may worsen thrombosis)

Contraindications: Heparin contraindicated in predominant bleeding DIC; tranexamic acid generally contraindicated

ICU: All DIC patients require ICU; sepsis resuscitation (antibiotics, source control); organ support; continuous monitoring of coagulation

19. 🟤 IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

Summary: Immune-mediated platelet destruction by anti-platelet antibodies (anti-GPIIb/IIIa); diagnosis of exclusion.

Investigations: CBC: isolated thrombocytopenia (↓platelets), normal WBC/Hb; blood film: large platelets, no other abnormalities; BM biopsy (if atypical): ↑megakaryocytes; DAT, antinuclear antibodies (exclude SLE); H. pylori testing

Findings: Petechiae, purpura, mucosal bleeding (epistaxis, gum bleeding), menorrhagia; spleen usually not enlarged; NO fever (distinguishes from TTP)

Differential Diagnosis: TTP/HUS, drug-induced thrombocytopenia (HIT, quinine), SLE, aplastic anemia, leukemia, hypersplenism

Treatment:

Platelet >30 without bleeding: observe
Prednisolone 1 mg/kg/day (first line)
IVIG 1 g/kg (rapid ↑platelets, for emergency/surgery)
Anti-D immunoglobulin (Rh+ patients)
Chronic/refractory: rituximab, splenectomy, thrombopoietin receptor agonists (eltrombopag, romiplostim)
H. pylori eradication if positive

Blood Transfusion: Platelet transfusion only in life-threatening bleeding (intracranial) — usually ineffective without IVIg coverage

Contraindications: Avoid NSAIDs and aspirin (worsen bleeding); splenectomy — ensure vaccinations (pneumococcal, meningococcal, Hib) 2 weeks prior

OPD: Monitor platelet count, taper steroids ICU: Intracranial hemorrhage → IVIg + methylprednisolone + emergency platelet transfusion ± emergency splenectomy

20. 🟤 THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

Summary: Deficiency of ADAMTS13 (vWF-cleaving protease) → ultra-large vWF multimers → platelet microthrombi → MAHA + thrombocytopenia.

Classic Pentad: Microangiopathic Hemolytic Anemia + Thrombocytopenia + Neurological symptoms + Renal impairment + Fever

Investigations: CBC: ↓Hb, ↓platelets; Blood film: schistocytes (key); ↑LDH, ↓haptoglobin, ↑bilirubin; ↑creatinine; Normal PT/APTT (distinguishes from DIC); ADAMTS13 activity <10% (diagnostic); ADAMTS13 inhibitor titer

Differential Diagnosis: HUS (↑creatinine predominant, ADAMTS13 normal), DIC, Evans syndrome, malignant hypertension, HELLP syndrome

Treatment: EMERGENCY

Plasma exchange (PEX) daily (removes inhibitor + replaces ADAMTS13) — start immediately
Corticosteroids (methylprednisolone)
Rituximab (anti-CD20) — for relapse/refractory
Caplacizumab (anti-vWF nanobody) — reduces recurrence

Contraindications: NEVER give platelet transfusion (fuels thrombosis — "adding fuel to fire"); heparin generally avoided

ICU: All TTP is ICU emergency; daily plasma exchange; intensive monitoring; seizure management

21. 🟤 HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)

Summary: Immune-mediated thrombocytopenia 5–10 days after heparin exposure; paradoxically causes thrombosis, not bleeding.

Investigations: 4T score (pre-test probability); anti-PF4/heparin antibodies (ELISA — sensitive but not specific); Serotonin release assay (gold standard — functional test); platelet count falls 50% from baseline

Findings: Thrombocytopenia + arterial/venous thrombosis, skin necrosis at heparin injection sites

Differential Diagnosis: Other drug-induced thrombocytopenia, TTP, post-transfusion purpura

Treatment:

Stop all heparin immediately (including flushes, LMWH, heparin-coated catheters)
Start non-heparin anticoagulant: argatroban, fondaparinux, bivalirudin, or danaparoid
Warfarin — only start after platelet recovery >150 (warfarin alone causes limb gangrene via protein C depletion)

Contraindications: All heparins contraindicated (including LMWH); avoid warfarin until platelets recover; platelet transfusion generally avoided

ICU: Anticoagulation with argatroban (hepatically metabolized); monitor ACT/APTT; manage thrombotic complications

22. 🟢 DEEP VEIN THROMBOSIS (DVT)

Summary: Thrombus in deep veins (usually lower limb); risk of pulmonary embolism.

Investigations: Wells score (pre-test probability); D-dimer (if Wells score low — to exclude); Duplex USS Doppler (first-line imaging); MRI venography (if proximal/pelvic); thrombophilia screen (if unprovoked, young, recurrent — FVL, prothrombin mutation, protein C/S, antithrombin, antiphospholipid)

Findings: Calf pain, swelling, pitting edema, warmth, redness; Homan's sign (unreliable)

Differential Diagnosis: Cellulitis, Baker's cyst, muscle tear, lymphedema, superficial thrombophlebitis

Treatment:

DOAC first-line: rivaroxaban (15 mg BD × 3 weeks, then 20 mg OD) or apixaban (10 mg BD × 7 days, then 5 mg BD)
LMWH → warfarin (INR 2–3) if DOACs unavailable or antiphospholipid syndrome
Duration: provoked — 3–6 months; unprovoked/recurrent — indefinite
Catheter-directed thrombolysis for massive iliofemoral DVT
Compression stockings (post-thrombotic syndrome prevention)

Contraindications: DOACs contraindicated in pregnancy (use LMWH), antiphospholipid syndrome (use warfarin), severe renal failure; avoid thrombolysis if recent surgery/stroke/active bleeding

OPD: INR monitoring (warfarin), thrombophilia workup, malignancy screen (unprovoked) ICU: Massive DVT with hemodynamic compromise — thrombolysis/thrombectomy; IVC filter if anticoagulation contraindicated

23. 🟢 PULMONARY EMBOLISM (PE)

Summary: Thromboembolic obstruction of pulmonary arteries → right heart strain, hypoxia, hemodynamic compromise.

Investigations: CTPA (gold standard); V/Q scan (renal impairment/pregnancy); D-dimer; ECG (S1Q3T3, sinus tachycardia, RBBB, right heart strain); Echo (RV dilation, McConnell sign); BNP/troponin (severity markers); ABG: hypoxia, hypocapnia, respiratory alkalosis

Findings: Pleuritic chest pain, dyspnea, tachycardia, hypoxia, hemoptysis (pulmonary infarction); massive PE → hemodynamic collapse, syncope, cardiac arrest

Differential Diagnosis: ACS, pneumonia, pneumothorax, aortic dissection, pericarditis, cardiac tamponade

Risk Stratification:

Massive (High-risk): SBP <90, cardiac arrest
Submassive: RV dysfunction + normal BP
Low-risk: hemodynamically stable

Treatment:

Massive PE: IV alteplase (systemic thrombolysis) + anticoagulation; surgical embolectomy if thrombolysis fails/contraindicated
Submassive/Low-risk: anticoagulation (DOACs, LMWH)
DOAC: rivaroxaban or apixaban
IVC filter: if anticoagulation absolutely contraindicated
Oxygen, IV fluids (cautious), vasopressors (norepinephrine) in shock

Contraindications: Thrombolysis contraindicated in: recent surgery <10 days, intracranial pathology, active bleeding, hemorrhagic stroke, uncontrolled hypertension

ICU: Massive PE — intubation (may worsen RV failure — avoid if possible), vasopressors, thrombolysis vs. ECMO vs. surgical embolectomy; avoid aggressive fluids (↑RV afterload)

24. 🟢 POLYCYTHEMIA VERA (PV)

Summary: JAK2 V617F mutation (>95%) → autonomous erythropoiesis → ↑RBC mass → hyperviscosity + thrombosis.

Investigations: CBC: ↑Hb (>16.5 M, >16 F), ↑Hct, ↑WBC, ↑platelets; JAK2 V617F mutation (key); ↓EPO; BM biopsy: hypercellular; Oxygen saturation normal (secondary polycythemia from hypoxia excluded)

Findings: Plethora, aquagenic pruritus (after hot bath — pathognomonic), hypertension, headache, blurred vision, splenomegaly, thrombosis (stroke, MI, Budd-Chiari), erythromelalgia (burning pain in hands/feet)

Differential Diagnosis: Secondary polycythemia (COPD, high altitude, EPO-secreting tumors), spurious polycythemia

Treatment:

Venesection (phlebotomy) — first line; target Hct <45%
Low-dose aspirin (antiplatelet, all patients)
Cytoreduction if high-risk (age >60, prior thrombosis): hydroxyurea (first line); ruxolitinib (JAK1/2 inhibitor) if hydroxyurea intolerant
Ropeginterferon-alfa (newer, potential disease modification)

Contraindications: Venesection contraindicated if Hct already controlled; high-dose aspirin — risk of major bleeding if platelets very high (>1000×10⁹/L)

OPD: Hematocrit monitoring, aspirin, thrombosis risk reduction ICU: Thrombotic events (stroke, MI, Budd-Chiari) — treat accordingly; extreme thrombocytosis → risk of bleeding

25. 🟢 ESSENTIAL THROMBOCYTHEMIA (ET)

Summary: Clonal myeloproliferative neoplasm; sustained ↑platelets (>450×10⁹/L); JAK2 (50–60%), CALR, MPL mutations.

Investigations: CBC: ↑platelets, normal RBC/WBC; JAK2/CALR/MPL mutation testing; BM biopsy (large mature megakaryocytes); rule out reactive thrombocytosis (iron deficiency, infection, inflammation)

Findings: Often asymptomatic; thrombosis (stroke, DVT, MI), bleeding (paradoxically at very high counts — acquired vWF deficiency), erythromelalgia, headache, transient visual disturbances

Differential Diagnosis: PV, reactive thrombocytosis, CML, MDS/MPN overlap

Treatment:

Low-risk (<60, no prior thrombosis, JAK2 wild-type): observe + aspirin
High-risk: hydroxyurea (cytoreduction) + aspirin; anagrelide (second line); interferon-α (pregnancy)

Contraindications: Anagrelide — cardiac side effects (palpitations, fluid retention); avoid high-dose aspirin if platelets >1500 (acquired vWF deficiency)

OPD: CBC monitoring, thrombosis/bleeding surveillance ICU: Thrombotic stroke, major bleeding

26. 🟢 MYELOFIBROSIS (MF)

Summary: Clonal myeloproliferative neoplasm with BM fibrosis → extramedullary hematopoiesis → massive splenomegaly.

Investigations: CBC: ↓Hb (anemia), ↑or↓WBC, ↑or↓platelets; Blood film: leukoerythroblastic picture, tear-drop cells (dacryocytes); BM biopsy: fibrosis (reticulin/collagen); JAK2 V617F, CALR, MPL mutations; LDH ↑; spleen USS

Findings: Massive splenomegaly (most prominent), constitutional symptoms (B symptoms), hepatomegaly (extramedullary), portal hypertension, bone pain, anemia symptoms

Differential Diagnosis: CML, other MPNs, secondary myelofibrosis, hairy cell leukemia

Treatment:

Symptomatic: ruxolitinib (JAK1/2 inhibitor) — reduces splenomegaly, improves symptoms
Pacritinib/momelotinib (for thrombocytopenic or anemic patients)
Allogeneic BMT (only curative option — in eligible patients with high-risk disease)
Supportive: transfusions, ESA (darbepoetin), splenectomy or splenic irradiation (for refractory splenomegaly/hypersplenism)

Blood Transfusion: Frequent pRBC; consider ESA; monitor for alloimmunization

Contraindications: Ruxolitinib — abrupt discontinuation causes cytokine storm (taper slowly); myelosuppression

ICU: Splenic infarction, blast transformation, severe infection

27. 🟠 ANEMIA OF CHRONIC DISEASE (ACD) / Anemia of Inflammation

Summary: Cytokine-mediated (IL-6 → ↑hepcidin → trapped iron) in chronic inflammatory states (RA, CKD, malignancy, IBD, HIV).

Investigations: CBC: normocytic or mildly microcytic anemia (Hb rarely <8); ↑ferritin, ↓serum iron, ↓TIBC, ↓transferrin saturation; Normal/↑hepcidin; ↑ESR/CRP (underlying disease)

Findings: Symptoms of chronic disease + mild-to-moderate anemia; NOT koilonychia, NOT glossitis

Differential Diagnosis: IDA (↓ferritin in IDA), mixed anemia, thalassemia

Treatment:

Treat underlying condition
ESA (erythropoietin alfa/darbepoetin) if CKD or malignancy-related
IV iron if concurrent IDA or pre-dialysis CKD
Blood transfusion if severe symptomatic anemia

Contraindications: ESA contraindicated in uncontrolled hypertension, active malignancy (↑thrombosis risk if Hb >12 g/dL target)

OPD: Disease-specific management; ESA dose titration ICU: Transfusion support for symptomatic anemia

28. 🟠 HEMOPHILIA A & B

Summary: X-linked recessive; Hemophilia A (↓Factor VIII), Hemophilia B (↓Factor IX — Christmas disease).

Investigations: ↑APTT, normal PT, normal platelets; Factor VIII or IX assay (confirms diagnosis); Inhibitor screen (anti-FVIII/FIX antibodies — complicates treatment); gene testing

Findings: Hemarthrosis (joints — pathognomonic), muscle hematomas, easy bruising; NO petechiae (platelet number/function normal)

Severity: Mild (FVIII/IX 5–40%), Moderate (1–5%), Severe (<1%)

Differential Diagnosis: Von Willebrand disease (↓APTT, ↓vWF), Factor XI deficiency, acquired hemophilia

Treatment:

Replacement: Factor VIII/IX concentrates (recombinant preferred); prophylaxis regimen vs. on-demand
Emicizumab (bispecific antibody mimicking FVIII — for Hemophilia A including inhibitors, SC weekly/every 2–4 weeks)
Desmopressin (DDAVP) — mild Hemophilia A only (releases stored FVIII/vWF)
Inhibitors: bypass agents (aPCC, rFVIIa); emicizumab
Gene therapy: emerging (etranacogene dezaparvovec approved for Hemophilia B)

Blood Transfusion: FFP (if concentrates unavailable); cryoprecipitate for Hemophilia A (rich in FVIII, vWF, fibrinogen)

Contraindications: Aspirin and NSAIDs absolutely contraindicated; IM injections contraindicated; avoid arterial punctures if possible; DDAVP ineffective in Hemophilia B

OPD: Hemophilia comprehensive care center; joint physiotherapy; inhibitor surveillance ICU: Life-threatening bleeds (CNS, airway, abdominal) — give factor concentrate immediately + ICU monitoring; inhibitor patients — rFVIIa or aPCC

29. 🟠 VON WILLEBRAND DISEASE (vWD)

Summary: Most common inherited bleeding disorder; deficiency or dysfunction of von Willebrand factor (vWF) → impaired platelet adhesion + ↓FVIII carrier.

Types:

Type 1 (75%): quantitative ↓, mild
Type 2: qualitative defects (2A, 2B, 2M, 2N)
Type 3: virtually absent vWF, severe

Investigations: ↑APTT (or normal), normal PT, ↓vWF antigen, ↓vWF ristocetin cofactor activity, ↓FVIII, ristocetin-induced platelet aggregation (RIPA); vWF multimer analysis (type 2 subtyping)

Findings: Mucocutaneous bleeding — epistaxis, menorrhagia, gum bleeding, easy bruising; hemarthrosis in Type 3 (mimics hemophilia)

Differential Diagnosis: Hemophilia A (↓FVIII only, normal vWF), ITP, platelet function disorders

Treatment:

DDAVP (desmopressin): Type 1 first line (IV/intranasal) — releases endogenous vWF; trial needed first
vWF concentrates (Humate-P, Wilate, Vonvendi/vonicog alfa)
Tranexamic acid: adjunct for mucosal bleeding (dental, menorrhagia)
Combined OCP: for menorrhagia in Type 1
Type 2B: DDAVP contraindicated (↑platelet aggregation → thrombocytopenia)

Blood Transfusion: Cryoprecipitate (contains vWF + FVIII) if concentrates unavailable

Contraindications: DDAVP contraindicated in Type 2B vWD, CVD (↑thrombosis), severe hyponatremia risk; aspirin/NSAIDs contraindicated

OPD: Pre-procedural planning, tranexamic acid for procedures ICU: Major surgical bleeding — continuous vWF/FVIII monitoring, repeat dosing

30. 🔵 BLOOD TRANSFUSION — Principles, Indications, Complications & Contraindications

Products & Indications

Product	Indication	Trigger
Packed Red Blood Cells (pRBC)	Symptomatic anemia, hemorrhage	Hb <7 (general); <8 (cardiac disease/ICU)
Fresh Frozen Plasma (FFP)	Coagulopathy (DIC, liver disease), massive transfusion	PT/APTT >1.5× normal
Cryoprecipitate	↓Fibrinogen (<1.5), Hemophilia A, vWD, DIC	Fibrinogen <1.5 g/L
Platelets	Bleeding + ↓platelets; prophylactic in severe thrombocytopenia	<10 (prophylactic); <50 (surgery/active bleeding)
Prothrombin Complex Concentrate (PCC)	Warfarin reversal, life-threatening bleeding	Urgent reversal of OAC
Albumin	Volume expansion, SBP, hepatic failure	Selected cases

Pre-Transfusion Checks

ABO/Rh group and cross-match
Confirm patient identity (2 identifiers at bedside)
Consent (elective), inform risks
Check irradiation (immunosuppressed), CMV-negative (at-risk), leukodepleted (all standard UK), warmed blood (massive transfusion)

Complications

Acute (<24h)	Delayed (>24h)
AHTR (ABO incompatibility — fever, rigors, hemoglobinuria, DIC)	DHTR (alloantibodies, +/- falling Hb at day 5–14)
Febrile non-hemolytic (most common — cytokines in stored blood)	Transfusion-associated iron overload (>20 units lifetime)
Allergic (urticaria → anaphylaxis — IgA deficiency)	Post-transfusion purpura (day 5–10, ↓platelets)
TRALI (non-cardiogenic pulmonary edema, dyspnea, hypoxia within 6h)	Transfusion-transmitted infections (HIV, HCV, HBV — rare)
TACO (cardiogenic pulmonary edema — use furosemide, slow rate)	Transfusion-associated graft-vs-host disease (TA-GvHD — irradiated blood prevents this)
Bacterial contamination (most common in platelets — fever, rigors, septic shock)
Hyperkalaemia, hypothermia, hypocalcaemia (massive transfusion)

ICU Transfusion Strategy

Restrictive strategy (Hb trigger 7–8) preferred over liberal in most ICU patients (TRICC/TRISS trials)
Massive transfusion protocol (MTP): 1:1:1 ratio pRBC:FFP:Platelets
Use TEG/ROTEM to guide hemostatic resuscitation
Permissive hypotension in trauma (target SBP 80–90 until surgical control)
Transfusion-associated circulatory overload (TACO) risk ↑in elderly, CKD, cardiac disease — give at 1 mL/kg/hr maximum, consider furosemide between units

Absolute Contraindications to Transfusion

ABO incompatibility (NEVER transfuse)
No consent in elective setting
Jehovah's Witness (respect autonomy; use cell salvage, ESA, IV iron alternatives)
Platelet transfusion in TTP and HIT (worsens outcome)

Relative Contraindications

Active febrile illness (delay non-urgent transfusion)
IgA deficiency without documented non-anaphylaxis (use IgA-deficient/washed blood)
CMV-seronegative immunosuppressed patients (use CMV-negative blood)
Patients at risk of iron overload (thalassemia — minimize unnecessary transfusions)

🏥 ICU vs. OPD Management Summary

Disease	ICU Priority	OPD Management
Aplastic anemia	Neutropenic sepsis, protective isolation, transfusion support	ATG + cyclosporine, CBC monitoring
AML	DIC, tumor lysis, febrile neutropenia	Induction chemo, BMT coordination
TTP	Daily plasma exchange, seizure control	ADAMTS13 monitoring, rituximab follow-up
DIC	Treat cause, replace factors (FFP/cryo/PLT)	Outpatient only after resolution
Massive PE	Thrombolysis, vasopressors, ECMO	DOAC × 3–6 months, thrombophilia screen
Sickle cell crisis	Exchange transfusion, O₂, opioids, hydration	Hydroxyurea, vaccines, prophylactic penicillin
Hemophilia (major bleed)	Immediate factor concentrate, ICU monitoring	Prophylactic factor infusions, inhibitor screen
Multiple myeloma	Hypercalcemia, AKI, hyperviscosity	VRd, bisphosphonates, IVIG
CML (blast crisis)	TKI + chemotherapy	TKI monitoring, BCR-ABL PCR
HIT	Stop heparin, argatroban	DOAC after platelet recovery

📋 Quick Differential Guide — Blood Disorders by Lab Pattern

Pattern	Think
Microcytic + ↓ferritin	Iron deficiency anemia
Microcytic + ↑ferritin + HbA₂ ↑	β-Thalassemia trait
Macrocytic + hypersegmented neutrophils	B12 or folate deficiency
Pancytopenia + hypocellular BM	Aplastic anemia
Pancytopenia + hypercellular BM + blasts	Leukemia/MDS
↓platelets only (isolated) + schistocytes	TTP or HUS
↓platelets only (isolated) + normal film	ITP
↑WBC + Philadelphia chromosome	CML
↑WBC lymphocytes + smudge cells	CLL
Leukoerythroblastic blood film + tear-drop cells	Myelofibrosis
Elevated M-protein + bone lesions	Multiple myeloma
↑Hct + ↓EPO + JAK2 mutation	Polycythemia vera
↑APTT + normal PT + hemarthrosis	Hemophilia A or B
↑APTT + normal PT + mucocutaneous bleeding	Von Willebrand disease
↑PT + ↑APTT + ↓fibrinogen + ↓PLT + ↑D-dimer	DIC
Thrombocytopenia + thrombosis after heparin	HIT

Sources: Harrison's Principles of Internal Medicine 22e; Robbins & Kumar Basic Pathology; Henry's Clinical Diagnosis and Management by Laboratory Methods; Goldman-Cecil Medicine; Tintinalli's Emergency Medicine; Washington Manual of Medical Therapeutics; Tietz Textbook of Laboratory Medicine.

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