Hematology System Study Guide

Anemia & Blood Disorders

Understanding Anemia

• Characterized by insufficient red blood cell levels in circulation
• Three primary mechanisms: Reduced RBC production, accelerated RBC breakdown, blood loss
• Clinical signs: Fatigue, weakness, dyspnea on exertion, decreased exercise tolerance
• Hemodynamic changes: Hypotension and tachycardia suggest significant volume depletion
• Hemoglobin below 12 g/dL typically indicates anemia
• Hematocrit represents RBC percentage of blood volume (normal approximately 40%)

Hypoproliferative Anemia (Decreased Production)

• Iron deficiency: Most common cause worldwide, check serum iron, transferrin, ferritin
• Renal disease: Damaged kidneys cannot produce adequate erythropoietin
• Erythropoietin stimulates RBC production in response to tissue hypoxia
• Chronic kidney disease requires exogenous erythropoietin (IV or subcutaneous)
• Nutritional deficiencies: Folic acid and vitamin B12 deficiency
• Bone marrow suppression: Chemotherapy, radiation, aplastic anemia

Hemolytic Anemia (Increased Destruction)

• Sickle Cell Disease: Genetic mutation causing abnormal hemoglobin and RBC sickling
• Sickle cell crisis: Vaso-occlusion leads to severe pain, ischemia, potential organ damage
• Crisis management: Opioid analgesia, aggressive hydration, exchange transfusion via apheresis
• Other causes: Transfusion reactions (ABO incompatibility), TTP, DIC
• Labs show elevated bilirubin, LDH, low haptoglobin, reticulocytosis

Anemia Diagnostics & Treatment

• Complete blood count: Hemoglobin, hematocrit, RBC indices (MCV, MCH, MCHC)
• Peripheral blood smear: Identifies abnormal RBC morphology
• Reticulocyte count: Assesses bone marrow response
• Blood conservation: Pediatric tubes, microtainers, minimize phlebotomy waste
• Treatment: Address underlying cause - supplements, EPO, transfusion if Hgb <7 g/dL

Coagulopathies Overview

Platelet Function & Disorders

• Platelets (thrombocytes) circulate for approximately 10 days
• Primary function: Aggregate at vessel injury sites to form initial clot
• Thrombocytopenia: Platelet count below 150,000/μL
• Causes: Drug-induced, heparin exposure, autoimmune, pregnancy-related, sepsis
• Critical threshold: Count below 10,000 with bleeding is a medical emergency
• Risk: Spontaneous intracerebral hemorrhage with severely low platelets

Immune Thrombocytopenic Purpura (ITP)

• Previously called Idiopathic Thrombocytopenic Purpura
• Autoimmune disorder: Antibodies destroy and inhibit platelet production
• Diagnosis: Isolated thrombocytopenia (<100,000) without identifiable cause, no anemia
• Presentation: Bleeding, petechiae, purpura (non-blanchable flat red lesions)
• Severity correlates with platelet count: Below 20,000 indicates greater bleeding risk
• Treatment: Platelet transfusion, IVIG, corticosteroids, tranexamic acid if refractory

Coagulation Testing

• PT/INR: Measures extrinsic pathway (factors VII, X, V, II, fibrinogen)
• aPTT: Measures intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, fibrinogen)
• Fibrinogen: Normal 200-400 mg/dL, consumed during clot formation
• D-Dimer: Fibrin degradation product, elevated with clot breakdown
• Thromboelastography (TEG): Point-of-care assessment of overall clot function

ITP vs HIT Clinical Distinction

• ITP: Primary risk is BLEEDING | HIT: Primary risk is THROMBOSIS
• ITP: Platelets indicated | HIT: Platelets contraindicated (worsen clotting)
• ITP: No medication trigger | HIT: Requires heparin exposure
• ITP: Variable onset | HIT: Typically 5-10 days post-heparin
• Both present with thrombocytopenia but clinical management differs drastically

Heparin-Induced Thrombocytopenia (HIT)

HIT Pathophysiology

• Life-threatening immune-mediated complication affecting approximately 5% of heparin-exposed patients
• Mortality rate approaches 20% if unrecognized or untreated
• Mechanism: Immune system generates antibodies against platelet factor 4 (PF4) bound to heparin
• These antibodies activate platelets causing aggregation and degranulation
• Paradox: Despite low platelets, hypercoagulable state develops
• Result: Simultaneous thrombocytopenia AND systemic thrombosis

Clinical Presentation & Timing

• Onset: Typically 5-10 days following heparin initiation
• Earlier onset possible with prior heparin exposure (rapid-onset HIT)
• Platelet decline: 50% or greater reduction from baseline
• Absolute count usually falls below 100,000/μL
• Thrombotic events: DVT, limb gangrene, pulmonary embolism, stroke, MI
• May also present with anaphylaxis following heparin bolus

4T Scoring System

• Thrombocytopenia: Degree of platelet decline (>50% drop scores highest)
• Timing: Onset relative to heparin exposure (days 5-10 scores highest)
• Thrombosis: Presence of new thrombotic events or skin necrosis
• Other causes: Alternative explanations for thrombocytopenia excluded
• Low probability score (<3): HIT unlikely
• Intermediate/High probability (4+): Requires testing and empiric treatment

Diagnostic Testing

• HIT ELISA panel: Detects anti-PF4/heparin antibodies
• Functional assay (SRA): Gold standard, confirms platelet-activating antibodies
• Clinical suspicion alone warrants empiric treatment
• Do not wait for laboratory confirmation before stopping heparin

HIT Management Protocol

• IMMEDIATE: Discontinue ALL heparin products (IV, SQ, flushes, coated catheters)
• Hold warfarin and reverse with vitamin K (slow IV infusion) until platelets recover
• Warfarin in acute HIT can cause skin necrosis and venous limb gangrene
• Initiate non-heparin anticoagulant: Argatroban (direct thrombin inhibitor) preferred
• Alternative agents: Bivalirudin, Fondaparinux in select cases
• Resume warfarin only after platelet count normalizes
• NEVER reintroduce heparin while antibodies persist (can last months)

Disseminated Intravascular Coagulation (DIC)

DIC Pathophysiology

• Also termed consumptive coagulopathy
• Normal hemostasis disrupted: Balance between clot formation and fibrinolysis fails
• Triggering events: Sepsis, trauma, obstetric emergencies, acute hemolytic reactions
• Procoagulants (bacterial endotoxins) tip balance toward excessive clot formation
• Systemic microthrombi consume platelets and fibrinogen
• Paradoxical result: MASSIVE clotting AND bleeding occur simultaneously

Laboratory Findings

• Fibrinogen: DECREASED (<1 g/L or <100 mg/dL) - consumed forming clots
• Platelets: DECREASED (<50,000) - trapped in microthrombi
• PT/aPTT: PROLONGED - clotting factors depleted
• D-Dimer: ELEVATED - marker of active fibrinolysis (not specific to DIC)
• Fibrin Degradation Products: ELEVATED
• Schistocytes on smear: Fragmented RBCs from microangiopathic hemolysis

Clinical Manifestations

• Bleeding: Oozing from IV sites, wounds, catheters, mucosal surfaces
• Skin findings: Petechiae, ecchymosis, purpura
• Thrombotic: Organ dysfunction from vascular occlusion
• Renal and hepatic dysfunction from ischemia
• Progression to shock and multi-organ failure
• Mortality rate: 40-80% depending on underlying cause

DIC Management Strategy

• Priority #1: Identify and treat underlying cause (sepsis, deliver fetus, stop incompatible transfusion)
• Hemodynamic support: Aggressive fluid resuscitation, vasopressors
• Ventilatory support as needed
• Blood products for active bleeding:
• - PRBCs for blood loss
• - Platelets if <50,000 with bleeding or <20,000 prophylactically
• - FFP to replace clotting factors
• - Cryoprecipitate for fibrinogen <100 mg/dL (concentrated fibrinogen source)
• Limited evidence supports antithrombotics like heparin in acute DIC

HELLP Syndrome

Understanding HELLP

• Acronym: Hemolysis, Elevated Liver enzymes, Low Platelets
• Affects up to 1% of pregnant and postpartum women
• Considered a severe variant of preeclampsia spectrum
• Preeclampsia: New-onset hypertension (>140/90) plus proteinuria during pregnancy
• Eclampsia: Preeclampsia with seizures
• HELLP represents life-threatening progression requiring urgent intervention

Clinical Presentation

• Right upper quadrant or epigastric pain (hepatic involvement)
• Hypertension: Systolic >140-160 mmHg
• Proteinuria on urinalysis
• Nausea and vomiting
• Headache and visual disturbances
• May present with non-specific flu-like symptoms

Diagnostic Criteria

• Hemolysis evidence:
• - Schistocytes on peripheral smear (fragmented RBCs)
• - Elevated bilirubin >1.2 mg/dL (from RBC breakdown)
• - Hemoglobin <8-10 g/dL not from blood loss
• Elevated liver enzymes: AST or ALT >2x upper normal limit
• - Normal AST: 10-40 U/L | Normal ALT: 5-50 U/L
• Low platelets: Count <100,000/μL

Management Priorities

• Antihypertensive therapy to prevent stroke:
• - IV Labetalol, Hydralazine, or Nicardipine
• Seizure prophylaxis with Magnesium Sulfate
• Stabilize maternal condition
• Definitive treatment: Delivery of fetus and placenta
• Transfuse PRBCs if hemoglobin <7 g/dL
• Transfuse platelets if count <20,000
• Supplemental oxygen as needed
• Close fetal monitoring until delivery

Complications & Monitoring

• Hepatic rupture or subcapsular hematoma
• Placental abruption
• DIC development
• Acute renal failure
• Pulmonary edema
• Stroke from uncontrolled hypertension
• Maternal and fetal mortality if untreated

TRALI vs TACO

Overview of Transfusion Pulmonary Complications

• Both present with acute respiratory distress during or after transfusion
• Both show bilateral pulmonary infiltrates on chest X-ray
• Critical to differentiate: Treatment approaches differ significantly
• Can occur with any blood component: PRBCs, platelets, FFP, cryoprecipitate
• TRALI: Immune-mediated lung injury
• TACO: Volume-related circulatory overload

TRALI (Transfusion-Related Acute Lung Injury)

• Mechanism: Donor antibodies react with recipient HLA or neutrophil antigens
• Results in pulmonary capillary leak and non-cardiogenic pulmonary edema
• Timing: Acute onset within 6 hours of transfusion
• Presentation: Sudden dyspnea, fever, HYPOTENSION
• Chest imaging: ARDS-like bilateral infiltrates
• Rare but potentially fatal complication

TACO (Transfusion-Associated Circulatory Overload)

• Mechanism: Volume exceeds cardiac output capacity
• More common than TRALI
• Risk factors: Cardiac/renal dysfunction, elderly, small body size
• Rapid infusion rate and multiple units increase risk
• Presentation: Dyspnea, HYPERTENSION, NO fever, rales/crackles
• Elevated BNP (B-type natriuretic peptide) supports diagnosis

Key Differentiating Features

• Blood pressure: TRALI = hypotension | TACO = hypertension
• Fever: TRALI = present | TACO = absent
• BNP: TRALI = normal/low | TACO = elevated
• Fluid balance: TRALI = euvolemic | TACO = positive/overloaded
• Ejection fraction: TRALI = preserved | TACO = may be reduced
• Response to diuretics: TRALI = minimal | TACO = improves

Management Strategies

• BOTH: Immediately stop transfusion, provide supplemental oxygen
• TRALI Treatment:
• - Supportive care with mechanical ventilation if needed
• - ARDS lung-protective ventilation protocol
• - Fluid resuscitation and vasopressors for hypotension
• TACO Treatment:
• - Diuretics (furosemide) to reduce volume overload
• - Upright positioning
• - Mechanical ventilation if respiratory failure

Prevention Approaches

• TRALI Prevention:
• - Screen blood donors for HLA antibodies
• - Use male-only plasma donors when possible
• TACO Prevention:
• - Slower transfusion rate (especially in at-risk patients)
• - Limit number of units when clinically appropriate
• - Consider prophylactic diuretics in cardiac patients
• - Frequent reassessment during transfusion

Hemorrhagic Shock Classification

Understanding Hemorrhagic Shock

• Results from acute blood loss exceeding compensatory mechanisms
• Hypovolemic shock subtype with hemorrhage as primary cause
• Severity based on estimated blood volume loss percentage
• Average adult blood volume: 70 mL/kg (approximately 5 liters)
• Early recognition essential: Mortality increases with severity class
• Treatment intensity escalates with each classification stage

Class I Hemorrhage (<15% Blood Loss)

• Blood volume lost: Up to 750 mL
• Heart rate: Within normal limits (stable)
• Blood pressure: Normal/stable
• Respiratory rate: Normal/stable
• Mental status: Slightly anxious
• Urine output: >30 mL/hr
• Management: Observation and monitoring
• Fluid resuscitation typically not required

Class II Hemorrhage (15-30% Blood Loss)

• Blood volume lost: 750-1500 mL
• Heart rate: 100-120 bpm (mild tachycardia)
• Blood pressure: Normal (diastolic may be elevated from vasoconstriction)
• Respiratory rate: Normal to mildly elevated
• Mental status: Mildly anxious
• Urine output: 20-30 mL/hr
• Management: Crystalloid resuscitation, possible transfusion
• Monitor response to initial fluid bolus

Class III Hemorrhage (30-40% Blood Loss)

• Blood volume lost: 1500-2000 mL
• Heart rate: >120 bpm (significant tachycardia)
• Blood pressure: Systolic <90 mmHg (HYPOTENSIVE)
• Respiratory rate: Elevated (tachypneic)
• Mental status: Anxious, confused
• Urine output: 5-15 mL/hr
• Management: Immediate blood transfusion indicated
• Aggressive crystalloid plus PRBCs

Class IV Hemorrhage (>40% Blood Loss)

• Blood volume lost: >2000 mL
• Heart rate: >140 bpm (severe tachycardia)
• Blood pressure: Markedly LOW (profound hypotension)
• Respiratory rate: Elevated, labored
• Mental status: Confused, lethargic, obtunded
• Urine output: Negligible
• Management: MASSIVE TRANSFUSION PROTOCOL immediately
• Life-threatening without immediate intervention

Massive Transfusion Protocol

• Definition: ≥10 units PRBCs in 24 hours OR ≥4 units in 1 hour
• Goal: Replace blood volume and prevent coagulopathy
• Balanced resuscitation: 1:1:1 ratio of PRBC:FFP:Platelets
• Prevents dilutional coagulopathy from crystalloid-heavy resuscitation
• Calcium replacement: Citrate in stored blood binds calcium
• Potassium monitoring: Stored PRBCs leak potassium
• Hypothermia prevention: Warm all blood products
• Point-of-care testing (TEG/ROTEM) guides ongoing transfusion

Transfusion Therapy & Reactions

Blood Product Indications

• PRBCs: Hemoglobin <7 g/dL (general), <8 g/dL (cardiac disease), active bleeding
• Platelets: <10,000 (prophylactic), <50,000 (bleeding/procedure), <100,000 (neurosurgery)
• FFP: Prolonged PT/INR with bleeding, warfarin reversal, DIC
• Cryoprecipitate: Low fibrinogen (<100-150 mg/dL), factor VIII deficiency
• Contains concentrated fibrinogen, factor VIII, vWF, factor XIII

Transfusion Reaction Types

• Febrile non-hemolytic: Most common, fever within 6 hours from donor leukocytes/cytokines
• Prevention: Leukoreduced blood products
• Allergic: Urticaria, itching - may give diphenhydramine and continue cautiously
• Anaphylactic: Severe hypotension, angioedema, bronchospasm - STOP immediately
• Treatment: Epinephrine, IV fluids, airway management

Acute Hemolytic Reaction

• Cause: ABO incompatibility (clerical error most common cause)
• Mechanism: Recipient antibodies rapidly destroy transfused RBCs
• Presentation: Fever, chills, tachycardia, hypotension, back/flank pain
• Hematuria (hemoglobinuria) - dark or red urine
• Consequences: Acute renal failure, DIC, hemodynamic collapse
• Management: STOP transfusion immediately, aggressive hydration, notify blood bank
• Send blood bag and tubing to lab for investigation

Metabolic Complications

• Hyperkalemia: Potassium leaks from stored RBCs (~1 mEq/L per day)
• Higher risk with massive transfusion, renal dysfunction
• Citrate toxicity: Citrate preservative binds calcium
• Results in hypocalcemia - monitor ionized calcium
• Symptoms: Tetany, prolonged QT, hypotension
• Treatment: Calcium gluconate replacement
• Hypothermia: Cold blood products decrease core temperature

Transfusion Safety Protocol

• Two-person verification of patient ID and blood product at bedside
• Baseline vital signs before starting transfusion
• Monitor vitals every 15 minutes initially, then hourly
• PRBCs: Infuse over 2-4 hours (maximum 4 hours to prevent bacterial growth)
• Platelets: Rapid infusion over 15-30 minutes
• FFP: Infuse over 30-60 minutes, must be ABO compatible
• For ANY suspected reaction: STOP transfusion, maintain IV, notify physician

White Blood Cell Disorders

Leukocyte Overview

• Normal WBC count: 4,000-11,000 cells/microliter
• Leukocytosis: Elevated WBC count (>11,000)
• Leukopenia: Decreased WBC count (<4,000)
• Five main types: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
• Differential count reveals which cell line is affected
• Left shift: Increased immature neutrophils (bands) - indicates acute infection

Neutrophils & Neutropenia

• Most abundant WBC (60-70% of circulating leukocytes)
• First responders to infection - phagocytosis of bacteria
• Absolute Neutrophil Count (ANC): Normal 2,500-7,500 cells/μL
• Neutrophilia (>7,700): Infection, inflammation, stress, steroids, malignancy
• Neutropenia (<1,500): High risk for serious infections
• Severe neutropenia (<500): Critical infection risk - requires protective precautions

Neutropenic Precautions

• Strict hand hygiene - most important intervention
• Private room with door closed when possible
• No fresh flowers or plants (harbor Aspergillus and bacteria)
• Avoid rectal temperatures, suppositories, enemas
• Low-microbial diet (no raw fruits/vegetables, unpasteurized products)
• Daily assessment for signs of infection - fever may be only sign
• Note: "Reverse isolation" terminology is outdated

Febrile Neutropenia Management

• Medical emergency: ANC <500 with fever (≥38.3°C or ≥38°C for 1 hour)
• Obtain cultures (blood, urine, sputum) but do NOT delay antibiotics
• Empiric broad-spectrum antibiotics within 1 hour of presentation
• Common regimen: Anti-pseudomonal beta-lactam (piperacillin-tazobactam, cefepime)
• Add vancomycin for catheter infection, skin/soft tissue involvement, or hemodynamic instability
• Antifungal coverage if fever persists >4-7 days
• G-CSF (filgrastim) may be used to stimulate neutrophil production

Lymphocytes & Lymphoproliferative Disorders

• Comprise approximately 30% of WBCs
• Types: T-cells, B-cells, Natural Killer (NK) cells
• Lymphocytopenia: HIV, immunosuppressants, chemotherapy, stress
• Lymphocytosis: Viral infections, chronic lymphocytic leukemia (CLL)
• Lymphadenopathy: Painless lymph node enlargement - concerning for malignancy
• Hodgkin and Non-Hodgkin lymphomas: Bone marrow malignancies
• Treatment: Chemotherapy, radiation, stem cell transplantation

Oncologic Emergencies

Tumor Lysis Syndrome (TLS)

• Massive release of intracellular contents when tumor cells are destroyed
• Most common with chemotherapy for hematologic malignancies
• High-risk: Acute leukemias, high-grade lymphomas, bulky tumors
• Occurs within 12-72 hours of initiating chemotherapy
• Oncologic emergency with significant mortality if untreated

TLS Metabolic Abnormalities

• Hyperkalemia: Potassium released from lysed cells - cardiac arrhythmia risk
• Hyperphosphatemia: Phosphorus released - binds calcium causing hypocalcemia
• Hypocalcemia: Secondary to hyperphosphatemia - tetany, seizures, arrhythmias
• Hyperuricemia: Nucleic acid breakdown → uric acid → crystallizes in renal tubules
• Results in acute kidney injury from urate nephropathy
• Calcium-phosphate product >60: Risk of tissue calcification

TLS Prevention & Monitoring

• Risk stratification before chemotherapy initiation
• Aggressive IV hydration: 2-3 L/m²/day to maintain high urine output
• Allopurinol: Inhibits xanthine oxidase, reduces uric acid formation
• Rasburicase: Converts uric acid to allantoin (more soluble) - for high-risk patients
• Avoid rasburicase in G6PD deficiency (causes hemolysis)
• Frequent lab monitoring: Q6-8 hours during high-risk period
• Monitor ECG for hyperkalemia and hypocalcemia changes

TLS Treatment

• Hyperkalemia: Calcium gluconate (cardiac protection), insulin/glucose, kayexalate
• Hyperphosphatemia: Phosphate binders (sevelamer, calcium carbonate)
• Hypocalcemia: IV calcium gluconate (cautiously if phosphorus still elevated)
• Hyperuricemia: Rasburicase if not already given, allopurinol
• Acute kidney injury: May require renal replacement therapy
• ICU admission for close monitoring and aggressive management

Leukemia Overview for Critical Care

• Acute leukemias: Rapid accumulation of immature blast cells
• AML (Acute Myeloid Leukemia): Most common acute leukemia in adults
• ALL (Acute Lymphoblastic Leukemia): More common in children
• Presentation: Pancytopenia (anemia, thrombocytopenia, neutropenia)
• Complications: Bleeding, infection, DIC, leukostasis
• Leukostasis: WBC >100,000 - medical emergency, risk of stroke/respiratory failure
• Chronic leukemias (CML, CLL): Generally less acutely symptomatic