ANEMIA

KEY POINTS
 DEFINITION: RBCs & Hb & PVC O2 delivery to the tissues compensated by (⇧O2 delivery , ⇧ EPO, ⇧ Plasma volume) affected by speed, severity & senility
 ClASSIFICTIONS: Etiological (Production, ⇧ Distruction, ⇧ Loss) & Morphological (Microcytic, Normocytic, Macrocytic)
 CP: General (Sx: {Geneal, CVS, Neuro, Genital} Sigs {Pallor, Hyperdynamic circ, LL edema}, Specific: related to cause

HEMOLYTIC ANEMIA
KEY POINTS
 DEFINITION: Premature destruction of the RBCs short life span maybe intravascular (PNH, G6PD, Allo-I, Some cases of AI, Infections, Physical, Chemical) or extravascular
 ETIOLOGY: Corpuscular (Membrane, Hb & Enzyme defects), Extra-corpuscular (Immune, Infection, Physical, Chemical, Hypersplenism, Metabolic)

Spherocytosis PNH Thalassemia Sickle cell anemia G6PD deficiency Auto immune
Etiology Deficiency of a protein Unknown Hb F Hb S Intravascular hemolysis of Warm' Cold
in the membrane of Abnormal membrane, AKA Cooley's anemia or on exposure to stress RBCs on exposure to Cold Paroxysmal
the RBCs →rigid small no CD55 & CD59 Mediterranean anemia or RBCs become sickle, less oxidizing stress due to Idiopathic
& spherical, more Triad of : Transfusion dependant anemia deformable deficiency of G6PD 2o(SLE, CLL, IMN, 2o to Syphilis
permeable to H2O pancytopenia, thrombosis, HA (hemolysis) ,vascular Lymphoma), Mycoplasma & Viral
⇧⇧Osmotic fragility occlusion Iatrogenic pneumonia
CP General Manifest. of anemia, general manifest of HJ (Jaundice, Dark stool, Normal urine), HSM, Gall stones, OJ, Leg ulcer, Crises (Hemolytic, Aplastic, Megaloplastic, Sequestrational, Vaso-Occlusive)
+FH, Childhood onset Intravascular hemolysis, Pain, +FH, Childhood onset, ⇧Fe, Vaso-occlusive crisis esp. Acute IV hemolysis Cause Raynaud's HA on
⇧Infection, Comp. IDA & Mongoloid face, Bone defects, Bone & Spleen, (Anemia, HJ, Hemoglobinuria), Phenomenon exposure to
Apalstic anemia & Stunted growth ⇧Infection, Hyposplenism Favism cold
Thrombosis
Investigations Of HA: CBC, Bone marrow, RBCs life span, Bile pigments, LDH Intra-vascular hemolysis: (Hemoglubinuria, Hemosiderinuria, Haptoglobin, Hemopexin)
⇧Osmotic fragility Ham test, Sucrose lysis test, Invest. for mycrocitic anemia , Hb electrophoresis (Hb Estimation of G6PD
test, Flow cytometry Hb electrophoresis (Hb F), S), Sickle cells + Invest. for IV hemolysis +ve Cooomb's test, For the cause
Microspherocytes + Invest. for IV hemolysis X-ray, Iron profile, Target cell
TTT Splenectomy & Sx (Androgens, Analgesics, Splenectomy Analgesics for Painfull crisis Avoid oxatadive stress, Corticosteroids, Cyclophosphamide,
Transfussion therapy Anticoagulant, ABs), Packed red cell transfusion, Desferrioxamine, Folic acid, Repeated Packed red cell Cyclophosphamide Transfusion,
Corticosteroids, BMT BMT, Gene therapy, Hydroxyurea, Prenatal diagnosis transfusion , Transfusion, Avoid cold exposure
Splenectomy

APLASTIC ANEMIA
KEY POINTS
 DEFINITION: anemia due to BM failure •ETIOLOGY: Aplastic anemia (Fanconi, Idiopathic {50%}, Iatrogenic, Infections, Insecticides, Irradiation, Immune, PNH,
Pregnancy)
Unicellular (Pure red cell aplasia, Granulocytopenia, Thrombocytopenia {TAR $})
 CP: Pancytopenia •INVESTIGATIONS: CBC, BM exam., For the cause •TTT: Supportive, Specific (BMT, Immunosupp.,
Androgens)

MEGALOPLASTIC ANEMIA
KEY POINTS
  DEFINITION: Anemia with impaired DNA synthesis due to Vit B12 & Folic acid
 ETIOLOGY: Vit B12 & Folic acid (Intake, Absorption, ⇧Demand, Folic acid antagonists) • CP: (Pancytopenia, HSM, Atrophic changes, SCD "B12", Ass. AI
disease)
 INVESTIGATIONS: CBC, BM exam., Serum B12 & Folic acid, Schilling test, FIGLU test, Therapeutic test •TTT: Replacement therapy, Transfusion, ttt of the cause
IRON DEFICIENCY ANEMIA, ANEMIA OF CHRONIC DISEASE & SIDEROBLASTIC ANEMIA
Iron deficiency anemia Anemia of chronic disease Sideroblasatic anemia
Definition Total Fe sufficient to erythropoiesis Anemia in chronic illness, Usually mild to moderate -------------------
The most common cause of anemia 2nd most common cause of anemia
Etiology Intake, Absorption, ⇧Demand, ⇧Loss (esp. GI) Chronic infection & Inflammation, Malignany Heridetary, Aquired (MDS Or 2o to RA, Malignancy, Lead)
Patho ------------------- Life span of RBCs, Impaired release of Fe, EPO defect Inability to use Fe in formation of Hb
CP 1.General Manifest. of anemia
2.Manifest. of Fe deficiency:
Atrophic changes,Mild splenomegaly
3.Manifest. of Specific type of Fe deficiency Of the cause + General Manifest. of anemia Microcytic hypochromic anemia
anemia:
A) Ancylostoma:
Loss of Fe & Prt, Abd. pain,eosinophilia & ova in
stool
B) Plummer- Vinson $
♀, Stomatitis, Spooning & Splenomegaly, Dysphagia
Investigations CBC, BM exam., Iron profile
(Fe, Ferritin & Tranferrin,⇧TIBC & FEP), Of the cause, Iron profile (Fe, ⇧ or normal Ferriten) Iron profile (⇧Fe,Ferriten & FEP) + Ringed sideroblasts in BM
For the cause (Stool, GIT Hge, Hemostatic disorders, CBC
MAS, Gastric function test)
TTT Specific ttt (cause, Replacement therapy), TTT of the cause, Recombinant EPO -------------------
Transfusion therapy, Symptomatic ttt

LEUKEMIAS
Acute leukemia Chronic leukemia
Acute myeloid leukemia Acute lymphatic leukemia Chronic myeloid leukemia Chronic lymphatic leukemia
CP BM failure, Manifest. of organ infiltration (Lymphadenopathy, HSM, Bone pain & sternal tenderness, Leukostasis, CNS {CN palsy, Focal paraplegia,
Meningeal irritation}, Hemoptysis, Hematuria, Pathological fractures, Joint effusion & arthritis, Ulcers & Hge,
Gums hypertophy, Rash & nodules, Polyserositis, Testicular swelling),
Metabolic manifest. (⇧ Uric acid, K, Na)
TAKE CARE: * CNS manifest. ALL>AML *Ulcers & Gums hypertophy common in Monoblastic leukemia * Testicular swelling common in ALL
*CML has 3 phases (Early asymptomatic in 80% of cases, Accelerated, Late Blastic crisis)
*Lymphadenopathy & organ infiltration are rare in CML *CLL asymptomatic in 25% of cases, Lymphadenopathy is the most important manifest.
I CBC WBCs: Leukocytosis RBCs: NN anemia Platelets: Thrombocytosis or Thrombocytopenia
n TLC: May reach 100,000/cmm Cells: Blasts TLC: May reach 100,000 - 1000,000/cmm
v Cells: Cytes except in Blast crisis Cells: Small lymphocytes
e BM Hypercellular BM è Blasts Hypercellular BM è Cytes except in .... Hypercellular BM è Small lymphocytes
s UA, LDH ⇧
t Vit B12 ⇧ 
DD Aplastic anemia, Fever with LN, Fever with sore throat, Rheumatic fever, CLL, Causes of huge splenomegaly, MPD CML, Causes of lymphocytosis &
Miliary TB Generalized LN enlargement
TTT Supportive, Chemotherapy ± radiotherapy, BMT if progressive, >45, Donor Supportive, Chemotherapy (Busulfan, Supportive, Chemotherapy
Hydroxyurea), Interferon α & TKIs, (Chlorambucil, Prednisone)
BMT if progressive, >30, Donor radiotherapy
POLYCYTHEMIA
KEY POINTS
 DEFINITION: ⇧Red cell mass >36 ml/Kg ♂ & >32 ml/Kg ♀
 ETIOLOGY: 2o (Chronic hypoxia, Cushing's, Renal disease, Paramalignant, Dehydration), PRV (MPD- RBCs mainly not only)
 CP: Plethora, Hperviscosity, Of the cause in 2o polycythemia, Manifest. of PRV (HSM, Pruritus), Complications of PRV (Thrombosis + Bleeding, PUD, HTN, ⇧Uric
a.)
 INVESTIGATIONS: CBC, Hypercellular BM, ESR, ⇧Red cell mass >36 ml/Kg ♂ & >32 ml/Kg ♀, ABG, Serum EPO, ⇧ LAP, ⇧ B12, ⇧ Uric acid
 TTT: PRV (Venesection, Chemotherapy (Hydroxyurea, Radioactive P, Busulphan), ttt of comp.) 2o Polycythemia (Venesection, ttt of cause)

IDIOPATHIC MYELOFIBROSIS
KEY POINTS
 DEFINITION: Progressive fibrosis of BM ass. è Myeloid metaplasia
 ETIOLOGY: Unknown Early (RBCs, ⇧ WBCs, ⇧ Megakaryocytess)⇧GFBM fibrosis Late: BM fibrosis Pancytopenia
 CP: Pancytopenia + HSM •INVESTIGATIONS: CBC, BM exam. (Fibrotic)
 TTT: Supportive (Transfusion, Splenectomy, Radiotherapy), Specific (Hydroxyurea, Stem cell transplatation)

LYMPHOMA
KEY POINTS
 DEFINITION: Neoplasm of B or T lymphocytes usually arising for LN maybe HD or NHL •ETIOLOGY: Unknown, PPF (Infection {EBV}, Irradiation,
Immunodeficiency)
 CP: Lymphadenopathy, HSM, Extra-lymphatic: General (Pel-Ebstein in HD, Fatigue, Weight loss, night sweats), Jaundice, MAS, GI Bleeding, Lung infiltration,
Pleural E, Focal CNS lesion, Pruritus, nodules, Hyperpigment, Bony pain & pathological fractures, Immunodeficiency, AIHA, AI thrombocytopenia.
 INVESTIGATION: LN & BM biopsy (in HD Reed sterberg cell), CBC (⇧TLC & lymphocytosis, AIHA or Myelopthisic anemia, AI thrombocytopenia), ⇧ESR, Imaging , β2 microglobulin, Staging laparotomy
 TTT:Radiotherapy (I or II A, For pressure manifest.) Chemotherapy (II B, III, IV, MOPP in HD, Cyclophosphamide, Doxorubicin, Oncovie, Prednisone)

MULTIPLE MYELOMA
KEY POINTS
 DEFINITION: Malignant proliferation of a single-clone of plasma cells in the BM leading to ⇧monoclonal Ig prt AKA "Paraprt or M prt or Bence-jones prt"
 CP: Bony pain & pathological fractures, AKI, CKD, Anemia, Bleeding, recurrent infection, Focal paraplegia, Fatigue, Weight loss, ⇧Ca
 INVESTIGATION: CT & x-ray, RFTs, Bence-jones proteinuria, CBC, ⇧Ca, SPEP, UPEP & Immunofixation, BM biopsy (Plasmacytosis)
 TTT: Chemotherapy (Melphalan, Thalidomide, Prednisone) Immunotherapy (Elotuzumab, Daratumumab) New therapy (Selinexor), Radiotherapy, BMT
 HYPOPROTHROMBINEMIA
KEY POINTS
 ETIOLOGY: LCF, Vit K, Hereditary • CP: Bleeding tendency + CP of the cause
 INVESTIGATIONS: Prolonged APTT & PT, Normal TT, Investigations for the cause • TTT: FFP, Parentral Vit K, ttt of the cause

HEMOSTATIC DISORDERS
Purpura Coagulpathy
Definition Bleeding tendency due to defect in Platelets or in Vessel wall Bleeding tendency due to defect in Coagulation factors
Etiology A) PLATELET DEFECT
1. Thrombocytopenia:
a) Decreased platelet production:
BM failure, BM infiltration, Megaloblastic anemia, MDS, PNH.
b) Increased platelet destruction: A) HEREDITARY
AI: 1o (ITP), 2o (SLE, CLL, Lymphoma, drugs as α-meth-d), • Hemophilia.
Acute infections, Hypersplenism, DIC, TTP, HUS. • Fibrinogen defect: Afibrinogenemia, Dysfibrinogenemia.
2. Thrombocytopathy: B) ACQUIRED
a) Hereditary: e.g. Glanzmann's disease. • Liver failure. • Renal failure.
b) Acquired: Uremia, MM, Thrombocytosis, Antiplatelet drugs, AI (SLE) • Deficiency of vitamin K. • DIC.
B) VESSEL WALL DEFECT (Vascular Purpura) • Drugs:Heparin, oral anticoagulants, fibrinolytic agents.
• Immune: Vasculitis e.g. SLE, PAN, Henoch-Schonlein purpura.
• Infection: SBE, meningococcemia.
• Iatrogenic: Salicylates, Sulphonamides, Penicillins, Corticosteroids.
• Idiopathic: Purpura simplex.
• Scurvy. • Senile purpura.
• Cushing's syndrome. • Congenital: Ehlers-Danlos
syndrome.
CP I. BLEEDING:
1. Site of bleeding:
• Orificial: epistaxis, melena, Hematochezia, HematemesisHemoptysis, Hematuria.
• Cutaneous: petichae, ecchymosis, excessive bleeding from wounds, + ve Hess test in purpura but -ve in Coagulpathy.
• MM: oral, gingival, conjunctival. • Internal: (intracranial hge, retinal hge, cavitary hge in Purpura + hemarthrosis, muscle hematoma in
coagulopathy).
2. Mechanism of bleeding: spontaneous or post-traumatic. 3. Character of bleeding: immediate in purpura & delayed in coagulopathy.
II.ANEMIA III,SHOCK IV.MANIFESTATION OF THE CAUSE
Investigations General investigations for hemostasis, CBC, BM examination, Coagulation factor assay, FDPs assay

IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

Acute ITP Chronic ITP
Etiology AI disease in which antiplatelet antibodies (usually IgG) directed against glycoprotein Ilb / IIIa of the platelets premature destruction of the platelets by MØ of the RES
Incidence Age: children. Sex: equal. Onset: acute. Age: yoyng adults & middle age. Sex:⇧♀ Onset: gradual.
Course: o 90 %: resolve spontaneously within 2 weeks to 6 months. Course:
o 10 %: develop chronic ITP (lasting > 6 months). o Prolonged for: months or years with remissions & exacerbations.
CP As Purpura
Investigations Platelets (Markedly in Acute ITP, Moderately in Chronic ITP), Prolonged BT, Normal (CT, PT, APTT, TT), BM (defective budding of megakaryocytes), Antiplatelets Abs
TT General Avoid trauma, Invasive procedures, antiplatelets
T Specific Prednisone, Platelets transfusion, IV gamma globulins Prednisone (Splenectomy , Cyclophos, Danazol if resestant), Platelets transfusion, IV γ globulins

HEMOPHILIA
KEY POINTS
 ETIOLOGY: X-linked hereditary AHG (Factor VIII) • CP: Since birth, ♂ , +ve FH, CP of coagulopathy
 INVESTIGATIONS: Prolonged CT & APTT, Normal (TT, PT, BT, Platelet count), AHG
 TTT: General (Avoid trauma, Invasive procedures, antiplatelets ), Specific (Factor VIII concentrates, FFP, Fresh blood, Local pressure, Hemathrosis)

THROMBOCYTOSIS
KEY POINTS
 ETIOLIGY: 1o: MPD è ⇧ Megakaryocytes in BM⇧ Platelets 2o: More common, Causes (Inflamation, Infection, Malignancy, Hge, Post-
splenectomy)
 CP: Thrombosis + Bleeding + Huge splenomegaly • INVESTIGATIONS: Platelet count > 1000,000/cmm è Hypercelllar BM
 TTT: Chemotherapy (Hydroxyurea, Radioactive P) Symptomatic ttt: Platelet-Phesesis

THROMBOPHILIA (HYPERCOAGULABILITY)
KEY POINTS
 DEFIINITION: Tendency to develop thrombosis due to abnormality of Coagulation system
 ETIOLOGY: I. Congenital: Homocysteinemia, Factor V Leiden, Prothrombin mutation, Deficiency of (protein C, protein S, Antithrombin III).
II. Acquired: Homocysteinemia, Antiphospholipid syndrome, SLE, PNH, DIC, MPD, Malignancy, Nephrotic syndrome,
Iatrogenic: (CCPs, Heparin - induced thrombocytopenia).

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

KEY POINTS
 DEFINITION: Abnormal activation of caogulation⇧ThrombosisPlatelets & clotting factorsBleeding tendency
 ETIOLOGY: Septicemia, Severe (Shock, Burn, Trauma, Hemolytic transfusion reactions), Advanced obstetric comp. (abruptio placenta, eclampsia), Malignancy
 CP: Bleeding + Thrombosis, MOSF (ARF, ARDS, Sepsis), MAHA
 INVESTIGATIONS: Prolonged (BT, CT, PT, APTT, TT), Platelets count & Fibrinogen level, ⇧FDPs
 TTT: ttt of the cause, ttt for bleeding (Platelets transfusion, FFP), ttt for thrombosis (Heparin)

HYPERSPLENISM
 KEY POINTS
 DEFINITION: Exaggeration of the normal splenic function  Monocytopenia or Bicytopenia or Pancytopenia • ETIOLOGY: Idiopathic or 2o
 CP: One or more of the following (Anemia, Bleeding, Fever è recurrent infections), Splenomegaly
 INVESTIGATIONS: CBC, BM exam., Cr. labeled RBCs, Investigations for the cause
 TTT: Splenectomy, Symptomatic ttt, ttt for the cause