Hematopoietic System

Etiology of Target Cells {HALT}

  • HbC disease
  • Asplenia
  • Liver disease
  • Thalassemia

Etiology of Anemia

Microcytic Anemia {TAILS}

Anemia Fe Ferritin Transferrin [TIBC] Saturation = Fe ÷ TIBC Defect
Thalassemia - - - - Hemoglobin
Anemia of chronic disease (ACD) - Fe
Iron deficiency anemia (IDA) Fe
Lead poisoning Heme
Sideroblastic anemia Heme

Normocytic Anemia

Non-hemolytic Anemia

  • Aplastic anemia
  • Chronic kidney disease (CKD)

Hemolytic Anemia

  Intravascular Extravascular
Peripheral smear Schistocyte Spherocyte
Haptoglobin -
Hemoglobin -
Hematuria + -
Indirect bilirubin -
Direct bilirubin - -
Urine bilirubin - -
Urine urobilinogen -
LDH
Jaundice - +
Intravascular Hemolytic Anemia {TIMP}
  • Transfusion
  • Infusion
  • Macroangiopathic hemolytic anemia (MAHA)
  • Microangiopathic hemolytic anemia (MAHA)
    • Disseminated intravascular coagulation (DIC)
    • Thrombotic thrombocytopenic purpura (TTP)
    • Hemolytic uremic syndrome (HUS)
    • HELLP syndrome
  • Paroxysmal nocturnal hematuria (PNH)
Extravascular Hemolytic Anemia {PHAGES}
  • Pyruvate kinase deficiency
  • HbC disease
  • Hereditary spherocytosis
  • Autoimmune hemolytic anemia (AHA)
  • G6PD deficiency
  • Elliptocytosis
  • Sickle cell disease (SCD)

Macrocytic Anemia

Megaloblastic

  • Folate deficiency
  • Vitamin B12 deficiency
  • Orotic aciduria
  • Fanconi anemia

Non-megaloblastic

  • Diamond-Blackfan anemia
  • Alcoholism
  • Reticulocytosis

Etiology of Elevated RDW

  • Iron deficiency anemia (IDA)
  • Folate deficiency anemia
  • Vitamin B12 deficiency anemia
  • Mixed anemia

Comparison Between Thalassemia and IDA

  Thalassemia IDA
Mentzer index = MCV ÷ RBC < 13 > 13
RDW -
Iron profile Normal Abnormal
Blood smear Target cells -

Etiology of Aplastic Anemia

  • Fanconi anemia
  • Virus
    • Parvovirus B19
    • EBV
    • CMV
    • HIV
    • Hepatitis virus
  • Drugs
    • Carbamazepine
    • Methimazole
    • Propylthiouracil
    • NSAIDs
    • Chloramphenicol
  • Toxins :: Benzene
  • Radiation

Presentation of Sickle Cell Disease (SCD)

  • Vaso-occlusive crisis (VOC)
  • Acute chest syndrome
  • Mesenteric ischemia
  • Ischemic stroke
  • Hemolysis :: extravascular
  • Splenic sequestration
  • Aplastic crisis
  • Avascular necrosis
  • Osteomyelitis
  • Dactylitis
  • Priapism

Triggers of Vaso-occlusive Crisis (VOC) in Sickle Cell Disease (SCD)

  • Dehydration
  • Infection
  • Hypoxia
  • Cold temperatures

Management of Sickle Cell Disease (SCD)

  • Immunizations
  • Penicillin prophylaxis
  • Folate supplementation
  • Transfusion
  • Hemapheresis
  • Hydroxyurea
  • Bone marrow transplantation

Treatment of Polycythemia

  • Phlebotomy
  • Antiplatelets :: Aspirin
  • Cytoreductive agents
    • Hydroxyurea
    • Interferon
    • Busulfan

Abnormal Hemoglobin Variants

  α-Globin Disease α-Globin Defect Disease
β-Globin α2β2 [HbA] - β4 [HbH] α-thalassemia :: 3 deletion
γ-Globin α2γ2 [HbF] β-thalassemia major γ4 [Hb Barts] α-thalassemia :: 4 deletion
δ-Globin α2δ2 [HbA2] β-thalassemia minor - -
s-Globin α2s2 [HbS] Sickle cell disease - -
c-Globin α2c2 [HbC] HbC disease - -

Heme Synthesis Disorders

  • Lead poisoning
  • Sideroblastic anemia
    • Alcoholism
    • ALA synthase deficiency
    • Vitamin B6 deficiency
    • Copper deficiency
  • Porphyria

Types of Porphyria

  • Acute intermittent porphyria (AIP)
  • Porphyria cutanea tarda (PCT)
  • Erythropoietic protoporphyria (EPP)

Presentation of Acute Intermittent Porphyria (AIP) {5P}

  • Pain :: abdomen
  • Port wine-colored urine
  • Peripheral neuropathy
  • Psychological disturbances
  • Precipitation
    • Starvation
    • Alcohol
    • Cytochrome P-450 (CYP450) inducers

Types of Transfusion Reactions

Type Causes Onset
Allergic Anti-plasma proteins IgE
Anti-IgA IgE
Minutes ~ Hours
Hemolytic (HTR) Anti-ABO
Anti-Rh
Minutes ~ Days
Febrile non-hemolytic (FNHTR) Cytokines Hours

Leukemia & Lymphoma

Myeloid Leukemia

Tumor Mutation Gene
AML t(15;17) PML/RARA
  t(8;21) RUNX1/RUNX1T1
  t(16;16) CBFB/MYH11
  - NPM1
  - CEBPA
  - FLT3
CML t(9;22) BCR/ABL1
  • Acute myelogenous leukemia (AML)
  • Chronic myelogenous leukemia (CML)

Lymphoid Leukemia

Tumor Mutation Gene
ALL t(12;21) ETV6/RUNX1
  t(1;19) TCF3/PBX1
  t(9;22) BCR/ABL1
  t(4;11) MLL/AF4
  Hyperdiploidy > 50 -
  Hypodiploidy < 44 -
CLL - -
HCL - -
  • Acute lymphocytic leukemia (ALL)
  • Chronic lymphocytic leukemia (CLL)
  • Hairy cell leukemia (HCL)

T-cell Lymphoma

Tumor Mutation Gene
Adult T-cell lymphoma - -
Cutaneous T-cell lymphoma - -

B-cell Lymphoma

Tumor Mutation Gene
Hodgkin lymphoma - -
Burkitt lymphoma t(8;14) C-MYC/IGH
Diffuse large B-cell lymphoma (DLBCL) - -
Marginal zone lymphoma
MALT lymphoma (MALToma)
- -
Mantle cell lymphoma t(11;14) Cyclin D (CCND)
Follicular lymphoma t(14;18) BCL2

Workup of Leukemia

  • Peripheral blood smear
  • Bone marrow smear
  • Cytochemistry
  • Immunophenotyping
  • Karyotyping
  • Genotyping

B Symptoms of Lymphoma

  • Fever
  • Night sweats
  • Weight loss

Treatment of Leukemia

Leukemia Treatment
AML Anthracyclines
Cytarabine
All-trans retinoic acid (ATRA)
CML Imatinib
ALL -
CLL Fludarabine
Cyclophosphamide
Rituximab
HCL Cladribine

Treatment of Hodgkin Lymphoma {ABVD}

  • Doxorubicin [Adriamycin]
  • Bleomycin
  • Vinblastine
  • Dacarbazine

Treatment of B-cell Non-Hodgkin Lymphoma {R-CHOP}

  • Rituximab
  • Cyclophosphamide
  • Doxorubicin [Hydroxydaunorubicin]
  • Vincristine [Oncovin]
  • Prednisolone

Causes of Monoclonal Spike [M Spike]

  • Multiple myeloma
  • Waldenstrom macroglobulinemia
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • AL amyloidosis

Presentation of Multiple Myeloma {CRAB}

  • Hypercalcemia
  • Renal failure
  • Rouleaux formation
  • Russell body
  • Anemia
  • Amyloidosis :: primary
  • Back pain
  • Bone lesions
  • Bence-Jones protein

Diagnostic Tests for Multiple Myeloma

  • Protein electrophoresis
  • Bone marrow biopsy
  • Skeletal survey

Diagnosis of Multiple Myeloma

  • Histology of bone marrow
    • Clonal bone marrow plasma cells > 10%
    • Plasmacytoma
  • Evidence of end-organ damages {CRAB}
    • Hypercalcemia
    • Renal failure
    • Anemia
    • Bone lesions
  • Evidence of inevitable end-organ damages
    • Free light chain (FLC) ratio > 100
    • Clonal bone marrow plasma cell > 60%
    • Bone lesions on MRI > 1

Presentation of Hemophagocytic Lymphohisticytosis (HLH)

  • Fever
  • ↑ Ferritin
  • Hypertriglyceridemia
  • Hemophagocytosis
  • ↓ NK cell activity
  • Pancytopenia
  • Rashes
  • Splenomegaly

Myeloproliferative Disorders

Tumors Genetics RBC WBC PLT
Polycythemia vera JAK2
Chronic myelogenous leukemia (CML) t(9;22)
Essential thrombocytosis JAK2 - -
Myelofibrosis JAK2 ↑/↓ ↑/↓

Coagulation Pathway

Enzymes Targeting Coagulation Factors

Enzyme Targets
VKOR ↑ Factor 2 & 7 & 9 & 10 & Protein C/S
Antithrombin ↓ Factor 2 & 7 & 9 & 10 & 11 & 12
Protein C/S ↓ Factor 5 & 8
Plasmin ↓ Factor 1

Virchow Triad for Thrombosis {SHE}

Cause Effect
Stasis VTE
Hypercoagulability ATE / VTE
Endothelial injury ATE

Etiology of Hypocoagulability

Etiology Mechanism PLT BT PT PTT Clots
Disseminated intravascular coagulation (DIC) - +
Thrombotic thrombocytopenic purpura (TTP) ↓ ADAMTS13 - - +
Hemolytic uremic syndrome (HUS) ↓ ADAMTS13
Shiga-like toxin
- - +
HELLP syndrome - - - -
Immune thrombocytopenic purpura (ITP) Anti-Gp1b
Anti-Gp2b/3a
- - -
Heparin-induced thrombocytopenia (HIT) Anti-platelet factor 4 (Anti-PF4) - - +
Antiphospholipid syndrome (APS) Anti-cardiolipin
Anti-β2-glycoprotein I
Lupus anticoagulant
- - - +
Von Willebrand disease (VWD) ↓ vWF - - -
Bernard-Soulier disease (BSD) ↓ Gp1b - - - -
Glanzmann disease ↓ Gp2b/3a - - - -
Hemophilia A & B & C ↓ Factor 8 & 9 & 11 - - - -
Vitamin K deficiency ↓ Factor 2 & 7 & 9 & 10 - - -
Cirrhosis ↓ Thrombopoietin (TPO)
↓ Factors
- -

Etiology of Hypercoagulability

Etiology Mechanism
Homocysteinemia ↑ Factor 7
Factor 5 Leiden mutation ↑ Factor 5
Prothrombin gene mutation ↑ Factor 2
Antithrombin deficiency ↓ Antithrombin
Protein C/S deficiency ↓ Protein C/S
Nephrosis ↓ Protein C/S
Pregnancy ↑ Factor 1

Antiplatelets

Mechanism Medication
Gp2b/3a inhibitors Abciximab
Eptifibatide
Tirofiban
ADP antagonists Clopidogrel
Prasugrel
Ticagrelor
Ticlopidine
PDE inhibitors Dipyridamole
Cilostazol
COX inhibitors NSAIDs

Anticoagulants

Mechanism Medication
VKOR inhibitors Warfarin
Coumadin
Antithrombin inducers Unfractionated heparin (UFH)
  Low-molecular-weight heparin (LMWH):
Enoxaparin
Dalteparin
  Fondaparinux
Factor 10a inhibitors Apixaban
Edoxaban
Rivaroxaban
Factor 2a inhibitors Hirudin
Bivalirudin
Argatroban
Dabigatran
Tissue plasminogen activators (tPAs) Urokinase
Streptokinase
Alteplase
Reteplase
Tenecteplase

Heparin Variants

  UFH LMWH
Bioavailability -
Half-life -
Specificity to Factor 10a -
Monitor PTT -
Side Effect HIT & Osteoporosis -
Antidote Protamine sulfate -

Goal INR

Condition INR
Venous thromboembolism (VTE) 2.0 ~ 3.0
Atrial fibrillation 2.0 ~ 3.0
Bioprosthetic valve 2.0 ~ 3.0
Mechanical valve 2.5 ~ 3.5

Management of Supratherapeutic INR

INR Management
< 4.5 Hold warfarin
4.5 ~ 10 Hold warfarin
Low-dose oral vitamin K
> 10 Hold warfarin
High-dose oral vitamin K
Bleeding Hold warfarin
High-dose IV viatamin K
FFP / PCC

Etiology of Disseminated Intravascular Coagulation (DIC)

Mnemonic Cause
S Sepsis :: GNB
T Trauma
O Obstetric complications
P Pancreatitis :: acute
Making Malignancy
New Nephrotic symdrome
Thrombi Transfusion

Pentad of Thrombotic Thrombocytopenic Purpura (TTP)

  • Renal symptoms
  • Anemia
  • Thrombocytopenia
  • Neurologic symptoms
  • Fever

Treatment of Thrombotic Thrombocytopenic Purpura (TTP)

  • Plasmapheresis
  • Immunosuppression
    • Corticosteroids
    • Rituximab

Triad of Hemolytic Uremic Syndrome (HUS)

  • Renal symptoms
  • Anemia
  • Thrombocytopenia

Treatment of Immune Thrombocytopenic Purpura (ITP)

  • Immunosuppression
    • Corticosteroids
    • Rituximab
  • Intravenous immunoglobulin (IVIG)
  • Splenectomy

Indications for Thrombolytics

  • ST-elevation myocardial infarction (STEMI)
    • Duration < 12 ~ 24 hours
    • Door-to-bolloon > 2 hours
  • Ischemic stroke
    • Duration < 3 ~ 4.5 hours
    • BP < 185/110 mmHg
  • Pulmonary embolism (PE)
    • Hemodynamic instability

Contraindications to Thrombolytics

  • Intracranial hemorrhage
  • Internal bleeding
  • Bleeding tendency

Plasma Products

  • Fresh frozen plasma (FFP)
  • Prothrombin complex concentrate (PCC)
  • Cryoprecipitate
  • Factor concentrate

Indications for Plasma Products

Product Indications
FFP / PCC Warfarin toxicity
Factor 10a inhibitors toxicity
Cryoprecipitate tPA toxicity
Fibrinogen deficiency
Hemophilia A
Von Willebrand disease (VWD)
Uremic bleeding
Factor concentrate Factor deficiency

Antifibrinolytics

  • Tranexamic acid
  • Aminocaproic acid