27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States

ABIM Critical Care Medicine Study Guide Exam

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1 Chapter 1: Exam Orientation: Format, Blueprint & Study Strategy

1.1 ABIM Critical Care Medicine Exam: Format, Blueprint & Study Strategy

2 Chapter 2: Acute Respiratory Failure & ARDS

2.1 ARDS Definition, Pathophysiology & Phenotypes 2.2 Lung-Protective Mechanical Ventilation 2.3 Refractory ARDS: Prone Positioning, Neuromuscular Blockade & VV-ECMO

3 Chapter 3: Obstructive Airways, Pulmonary Vascular & Pleural Emergencies

3.1 Severe Asthma & COPD Exacerbations in the ICU 3.2 Massive & Submassive Pulmonary Embolism 3.3 Pulmonary Hypertension & Right Ventricular Failure in the ICU 3.4 Massive Hemoptysis, Complex Pleural Effusions & Thoracic Drainage

4 Chapter 4: Airway, Parenchymal & Nonthrombotic Pulmonary Emergencies

4.1 Airway Management, Upper-Airway Obstruction & Artificial-Airway Complications 4.2 Diffuse Alveolar Hemorrhage, Interstitial Lung Disease, Pulmonary Vasculitis & Noncardiogenic Edema 4.3 Severe Community-Acquired & Viral Pneumonia 4.4 Nonthrombotic Embolism (Air, Fat, Amniotic Fluid, Tumor, Septic) & Acute Chest Syndrome

5 Chapter 5: Mechanical Ventilation Modes, Dyssynchrony & Liberation

5.1 Mechanical Ventilator Modes & Advanced Breath Delivery 5.2 Patient-Ventilator Dyssynchrony & Waveform Analysis 5.3 Ventilator Liberation, Spontaneous Breathing Trials & Post-Extubation Support

6 Chapter 6: Shock Syndromes & Hemodynamic Principles

6.1 Shock Classification, Cellular Pathophysiology & Biomarkers 6.2 Hemodynamic Monitoring: Arterial Lines, CVP & Pulmonary Artery Catheter 6.3 Dynamic Assessment of Fluid Responsiveness & Resuscitation Targets

7 Chapter 7: Vasoactive Therapies & Mechanical Circulatory Support

7.1 Vasopressors & Inotropes: Pharmacology & Clinical Titration 7.2 Temporary Mechanical Circulatory Support: IABP, Impella & TandemHeart 7.3 Venoarterial ECMO (VA-ECMO) & Differential Hypoxemia 7.4 Post-Cardiac Arrest Care, Targeted Temperature Management & Neuroprognostication

8 Chapter 8: Acute Kidney Injury & Renal Replacement Therapy

8.1 KDIGO AKI Classification, Etiologies & Diagnostic Evaluation 8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis 8.3 Indications & Timing for RRT in Critical Illness: AKIKI & STARRT-AKI

9 Chapter 9: Electrolyte, Acid-Base & Endocrine Emergencies

9.1 Severe Dysnatremias: Hyponatremia, Hypernatremia & Osmotic Demyelination 9.2 Potassium, Calcium, Magnesium & Phosphate Disorders 9.3 Complex & Mixed Acid-Base Disorders: Boston vs Copenhagen vs Stewart 9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis

10 Chapter 10: Glycemic Control, Hyperammonemia, Pituitary & Adrenal Disorders

10.1 ICU Glycemic Control & Severe Hypoglycemia 10.2 Non-Hepatic Hyperammonemia & Metabolic Encephalopathy 10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency

11 Chapter 11: Acute Coronary Syndromes & Cardiac Arrhythmias

11.1 Acute Coronary Syndromes & Mechanical Complications of Myocardial Infarction 11.2 Critical Tachyarrhythmias: Atrial Fibrillation with RVR, VT & VF 11.3 Critical Bradyarrhythmias, Conduction Blocks & Temporary Cardiac Pacing

12 Chapter 12: Acute Heart Failure, Valvular & Pericardial Emergencies

12.1 Acute Decompensated Heart Failure & Cardiogenic Pulmonary Edema 12.2 Acute Valvular Regurgitation & Prosthetic Valve Emergencies 12.3 Pericardial Tamponade & Acute Aortic Syndromes

13 Chapter 13: Myocardial Disease, Hypertensive & Cardiac Device Emergencies

13.1 Fulminant Myocarditis, Stress & Peripartum Cardiomyopathy, and Hypertrophic Cardiomyopathy 13.2 Hypertensive Emergencies & Ruptured Abdominal Aortic Aneurysm 13.3 Implanted Cardiac Devices, LVAD Emergencies & Electrical Storm

14 Chapter 14: Sepsis & Systemic Infectious Diseases

14.1 Sepsis-3 Definitions & Surviving Sepsis Campaign 2026 Guidelines 14.2 Refractory Septic Shock & Adjunctive Therapies 14.3 Multidrug-Resistant Pathogens & Antimicrobial Stewardship in the ICU

15 Chapter 15: ICU-Acquired & Severe Focal Infections

15.1 Hospital-Acquired & Ventilator-Associated Pneumonia 15.2 Central Line-Associated Bloodstream Infections & Catheter-Associated UTIs 15.3 Intra-Abdominal Sepsis, Necrotizing Soft Tissue Infections & CNS Infections

16 Chapter 16: Focal, Special-Host & Systemic Infections

16.1 CNS Infections Beyond Bacterial Meningitis: Encephalitis, Brain Abscess & Epidural Abscess 16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections 16.3 Infective Endocarditis, Device Infections & Other Focal Cardiovascular Infections 16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention 16.5 Gastrointestinal & Hepatobiliary Infections: Fulminant C. difficile, Typhlitis, CMV Colitis & Abscesses

17 Chapter 17: Neurocritical Care & Coma

17.1 Coma, Altered Mental Status & Acute Delirium in the ICU 17.2 Status Epilepticus & Non-Convulsive Status Epilepticus 17.3 Acute Ischemic Stroke & Intracranial Hemorrhage

18 Chapter 18: Cerebrovascular Syndromes, Encephalopathy & Withdrawal States

18.1 Cerebral Venous Sinus Thrombosis, PRES & Reversible Cerebral Vasoconstriction Syndrome 18.2 Alcohol & Sedative Withdrawal, Wernicke Encephalopathy & Drug-Induced Encephalopathy

19 Chapter 19: Intracranial Hypertension & Neuromuscular Weakness

19.1 Intracranial Pressure Monitoring, Cerebral Perfusion & Tiered ICP Management 19.2 Acute Neuromuscular Respiratory Failure, ICU-Acquired Weakness & Brain Death Determination

20 Chapter 20: Traumatic Brain Injury, Spinal Cord Injury & Toxin-Mediated Paralysis

20.1 Traumatic Brain Injury Management & Paroxysmal Sympathetic Hyperactivity 20.2 Acute Spinal Cord Injury, Neurogenic Shock & Autonomic Dysreflexia 20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis

21 Chapter 21: Gastrointestinal, Hepatic & Abdominal Emergencies

21.1 Acute Upper & Lower Gastrointestinal Bleeding in the ICU 21.2 Acute Liver Failure & Severe Acute Pancreatitis 21.3 Abdominal Compartment Syndrome & Acute Mesenteric Ischemia

22 Chapter 22: Luminal GI Emergencies & Complications of Cirrhosis

22.1 Esophageal, Gastric & Bowel Emergencies: Perforation, Obstruction, Ogilvie Syndrome & Colonic Ischemia 22.2 Complications of Cirrhosis: Alcohol-Associated Hepatitis, Hepatorenal Syndrome & Pulmonary Vascular Syndromes

23 Chapter 23: Trauma, Burns & Perioperative Critical Care

23.1 Polytrauma Resuscitation, Damage Control & Massive Transfusion 23.2 Severe Burn Injury, Inhalation Injury & Environmental Emergencies 23.3 Perioperative Critical Care for High-Risk Surgical Patients

24 Chapter 24: Thoracic Trauma, Environmental Injury & Obstetric Critical Care

24.1 Thoracic Trauma: Flail Chest, Pulmonary Contusion, Great Vessel & Tracheobronchial Injury 24.2 Environmental Injury: Drowning, Diving, Altitude, Heat, Cold, Electrical & Radiation 24.3 Obstetric & Genitourinary Emergencies and the Physiology of Pregnancy

25 Chapter 25: Transplantation, Donor Management & Post-Cardiac Surgery Care

25.1 Solid Organ Transplant Recipients & Deceased Donor Management 25.2 Post-Cardiac Surgery Critical Care: Bleeding, Tamponade, Low Output & Vasoplegia

26 Chapter 26: Hematologic Emergencies, Toxicology, Critical Ultrasound & ICU Liberation

26.1 Hematologic Emergencies in the ICU: HIT, DIC, TMA & Anticoagulant Reversal 26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes 26.3 Critical Care Point-of-Care Ultrasound (POCUS) 26.4 ICU Liberation, Analgosedation, Goals of Care & Critical Care Ethics

27 Chapter 27: Transfusion Medicine, Hematologic & Oncologic Disorders

27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis 27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States 27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity

28 Chapter 28: Clinical Pharmacology, Adverse Drug Reactions & Specific Poisonings

28.1 Pharmacokinetic Principles, Dose Adjustment & Drug Interactions in Critical Illness 28.2 Adverse Drug Reactions: Anaphylaxis, Severe Cutaneous Reactions & Hyperthermic Syndromes 28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia

29 Chapter 29: Ethics, Research Methods, Administration & Abdominal Ultrasound

29.1 Advance Care Planning, Nonbeneficial Treatment, Informed Consent & Confidentiality 29.2 Critical Care Research Methods, Statistics, IRB Oversight & Quality Improvement 29.3 Abdominal, Vascular & Procedural Point-of-Care Ultrasound

27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States

Key Takeaways Explain This Topic AI

Leukostasis is a clinical diagnosis in hyperleukocytosis with respiratory or neurologic symptoms; red cell transfusion raises viscosity and should be deferred until the white count falls.

Hemophilia A with life-threatening bleeding is treated by raising factor VIII activity to 80% to 100%, with each unit per kilogram raising activity by about 2%.

Acquired hemophilia A presents with a prolonged aPTT that fails to correct on mixing study and is treated with bypassing agents plus immunosuppression.

Catastrophic antiphospholipid syndrome involves three or more organ systems within a week and is treated with anticoagulation, corticosteroids, and plasma exchange or IVIG.

Direct antiglobulin testing separates autoimmune hemolysis (warm or cold) from microangiopathic hemolysis, where schistocytes dominate and the test is negative.

Last updated: October 2026

Anemia in the Critically Ill

Causes overlap: blood loss (including phlebotomy, which can exceed 40 mL/day), hemodilution, inflammation-driven suppressed erythropoiesis with functional iron restriction, nutritional deficiency, kidney failure, hemolysis, and marrow suppression by drugs or infection.

Work the hemolysis question explicitly :

Supporting findings: elevated LDH and indirect bilirubin, low haptoglobin , reticulocytosis, and a falling hemoglobin out of proportion to blood loss.

Direct antiglobulin (Coombs) test : positive in autoimmune hemolysis.

Warm (IgG) : spherocytes; idiopathic, lymphoproliferative disease, lupus, drugs (cephalosporins, penicillins, quinine). Treat with corticosteroids , then rituximab, IVIG, or splenectomy.

Cold (IgM agglutinin) : acrocyanosis and agglutination on the smear; Mycoplasma , EBV, and lymphoma. Keep the patient warm ; steroids are less effective, and rituximab or complement inhibition is used.

Negative antiglobulin test with schistocytes : microangiopathic hemolysis (TTP, hemolytic uremic syndrome, disseminated intravascular coagulation, HELLP, mechanical valve or device hemolysis, malignant hypertension).

Other patterns : G6PD deficiency with bite cells and Heinz bodies after oxidative stress (rasburicase, dapsone, primaquine, nitrofurantoin, methylene blue, infection); hyperhemolysis after transfusion in sickle cell disease.

Erythropoiesis-stimulating agents are not recommended for routine ICU anemia; treat iron deficiency when documented.

Polycythemia : distinguish relative (hemoconcentration) from absolute. Polycythemia vera (JAK2 mutation) causes thrombosis, including splanchnic vein thrombosis; treat acute hyperviscosity with phlebotomy and antiplatelet therapy, plus cytoreduction. Secondary polycythemia follows chronic hypoxemia, high-altitude residence, obstructive sleep apnea, or erythropoietin-secreting tumors.

Hemoglobinopathies

Sickle cell disease crises in the ICU :

Vaso-occlusive pain crisis : opioids by protocol, hydration (avoid overload), oxygen only for hypoxemia, incentive spirometry to prevent acute chest syndrome, and treatment of triggers.

Acute chest syndrome (see the pulmonary section).

Stroke : exchange transfusion plus standard stroke care.

Splenic sequestration and aplastic crisis (parvovirus B19): transfusion support.

Priapism, renal papillary necrosis, hepatic crisis, and multiorgan failure also occur.

Fat embolism from marrow infarction can cause rapid multiorgan failure, treated with exchange transfusion.

Thalassemia : transfusion dependence with iron overload (cardiac and hepatic), extramedullary hematopoiesis, and infection risk after splenectomy.

Methemoglobinemia and carboxyhemoglobinemia are covered in the toxicology sections; remember that a "saturation gap" between pulse oximetry and the measured arterial oxygen saturation signals a dyshemoglobinemia.

White Cell Disorders

Neutropenia : chemotherapy, drugs (clozapine, propylthiouracil, methimazole, sulfasalazine, vancomycin, linezolid), autoimmune disease, and marrow failure. Treat fever immediately (see the neutropenic fever section).

Hyperleukocytosis and leukostasis :

A white cell count above about 100,000/µL (lower thresholds matter in acute myeloid leukemia with blasts, which are less deformable than lymphoblasts).

Leukostasis is a clinical diagnosis: dyspnea and hypoxemia (often with clear radiographs), confusion, visual changes, headache, and priapism.

Treatment : aggressive hydration, prompt cytoreduction (hydroxyurea or induction chemotherapy), tumor lysis prophylaxis with allopurinol or rasburicase, and leukapheresis for symptomatic leukostasis. Avoid red cell transfusion until the count falls, because it increases viscosity; transfuse platelets freely to reduce hemorrhage risk.

Acute promyelocytic leukemia is a special case: start all-trans retinoic acid immediately on suspicion because of the coagulopathy, support fibrinogen and platelets aggressively, avoid leukapheresis (which can worsen bleeding), and watch for differentiation syndrome (fever, hypoxemia, infiltrates, weight gain) treated with dexamethasone.

Hematologic malignancies in the ICU : outcomes have improved substantially, so critical care should not be withheld on diagnosis alone. Watch for tumor lysis, infection with unusual organisms, hyperviscosity in myeloma and Waldenström macroglobulinemia, and spinal cord compression.

Hemophagocytic lymphohistiocytosis : fever, splenomegaly, cytopenias, very high ferritin , high triglycerides, low fibrinogen, and high soluble CD25; triggered by infection (EBV), malignancy, or autoimmune disease. Treat the trigger with steroids, etoposide, or anakinra; it is frequently mistaken for sepsis.

Factor Deficiencies and Acquired Coagulopathies

Disorder Laboratory pattern Treatment of major bleeding

Hemophilia A (factor VIII) Prolonged aPTT, normal PT, corrects on mixing Factor VIII concentrate to 80% to 100% activity (1 unit/kg raises activity about 2%), then maintenance; emicizumab-treated patients need specialist guidance; desmopressin for mild disease

Hemophilia B (factor IX) Prolonged aPTT Factor IX concentrate (1 unit/kg raises activity about 1%)

Inhibitors in hemophilia Factor levels fail to rise Bypassing agents : activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa

Acquired hemophilia A Prolonged aPTT that does not correct on mixing study ; often older adults, postpartum, malignancy, or autoimmune disease Bypassing agents for bleeding plus immunosuppression (steroids with cyclophosphamide or rituximab)

von Willebrand disease Prolonged aPTT in severe types, abnormal platelet function Desmopressin (type 1), von Willebrand factor-containing concentrate (types 2 and 3); avoid desmopressin in type 2B

Vitamin K deficiency Prolonged PT first, then aPTT; common in ICU patients on antibiotics with poor intake Vitamin K 10 mg; 4-factor PCC for major bleeding

Liver failure coagulopathy Global factor deficiency with reduced anticoagulants: rebalanced hemostasis Do not correct the INR prophylactically; use fibrinogen and targeted products for bleeding

Uremic platelet dysfunction Normal count, abnormal function Desmopressin, cryoprecipitate, dialysis, conjugated estrogens

Factor XIII deficiency Normal PT and aPTT with delayed bleeding and poor wound healing Factor XIII concentrate or cryoprecipitate

Isolated prolonged aPTT in the ICU: consider heparin contamination, lupus anticoagulant (usually thrombotic rather than bleeding), factor deficiency, or an acquired inhibitor. A mixing study separates deficiency (corrects) from inhibitor (does not correct).

Hypercoagulable States

Disorder Features

Factor V Leiden Most common inherited thrombophilia in people of European ancestry; activated protein C resistance

Prothrombin G20210A Second most common

Protein C, protein S, and antithrombin deficiency Antithrombin deficiency causes heparin resistance; protein C deficiency predisposes to warfarin-induced skin necrosis when warfarin is started without bridging

Antiphospholipid syndrome Arterial and venous thrombosis, pregnancy loss, thrombocytopenia, prolonged aPTT with a positive lupus anticoagulant, anticardiolipin, or anti-beta-2-glycoprotein I antibody. Use warfarin , not direct oral anticoagulants, especially in triple-positive or arterial disease

Malignancy Trousseau syndrome; use low-molecular-weight heparin or selected direct oral anticoagulants, avoiding the latter with luminal gastrointestinal or genitourinary tumors

Heparin-induced thrombocytopenia See the hematologic emergencies section

Paroxysmal nocturnal hemoglobinuria Hemolysis with thrombosis, including splanchnic and cerebral veins; treat with complement inhibition

Nephrotic syndrome, inflammatory bowel disease, hormonal therapy, pregnancy, immobility, and COVID-19 Acquired risk factors

Catastrophic antiphospholipid syndrome is defined by involvement of three or more organ systems within a week with histopathologic evidence of small-vessel occlusion and persistent antiphospholipid antibodies. Mortality is high. Treatment combines therapeutic anticoagulation, high-dose corticosteroids, and plasma exchange or IVIG , with rituximab or eculizumab in refractory cases, plus treatment of any trigger such as infection or anticoagulation interruption.

Testing caution in the ICU : acute thrombosis, heparin, warfarin, and acute illness distort thrombophilia assays. Antithrombin, protein C, and protein S are consumed acutely; lupus anticoagulant testing is unreliable on anticoagulants. Defer most thrombophilia testing until the patient has recovered, except where it changes immediate management (such as suspected catastrophic antiphospholipid syndrome or heparin-induced thrombocytopenia).