Causes of Increased aPTT + Thrombocytopenia

1. Disseminated Intravascular Coagulation (DIC)

• Sepsis (most common)
• Trauma / burns
• Obstetric emergencies (abruption, amniotic fluid embolism, dead fetus syndrome)
• Acute promyelocytic leukemia (APL / AML-M3)
• Malignancy (solid tumors)
• Transfusion reactions

2. Heparin Therapy + Heparin-Induced Thrombocytopenia (HIT)

• Heparin directly prolongs aPTT (its intended action)
• HIT (Type II): immune-mediated platelet destruction via anti-PF4/heparin antibodies → thrombocytopenia (typically 50% drop from baseline, days 5–10 of therapy)
• Paradoxically pro-thrombotic despite low platelets

3. Antiphospholipid Syndrome (APS)

• aPTT is paradoxically prolonged in vitro (lupus anticoagulant interferes with phospholipid-dependent clotting assays) — yet the patient is pro-thrombotic
• Thrombocytopenia occurs in ~20–40% of cases (immune-mediated platelet destruction)
• Associated with: SLE, recurrent thrombosis, recurrent miscarriages
• Key test: mixing study (aPTT does NOT correct), confirm with dilute Russell viper venom time (dRVVT)

4. Severe Liver Disease

• Mechanism: Reduced synthesis of all clotting factors (prolonged aPTT) + platelet sequestration from portal hypertension/hypersplenism
• Unlike DIC, lab parameters change slowly (helpful distinguishing feature)
• D-dimer may be mildly elevated
• (Harrison's, p. 3481)

5. Thrombotic Thrombocytopenic Purpura (TTP)

• Thrombocytopenia is prominent (microangiopathic platelet consumption)
• aPTT/PT are usually normal in classic TTP, but can be prolonged in severe cases
• Key features: microangiopathic hemolytic anemia (MAHA), schistocytes on smear, neurological symptoms, renal impairment, fever
• ADAMTS13 activity markedly reduced (<10%)
• (Harrison's, p. 3481)

6. Massive Transfusion / Dilutional Coagulopathy

• Large-volume crystalloid or pRBC transfusion dilutes clotting factors → prolonged aPTT
• Dilutes platelets → thrombocytopenia
• Manage with FFP, cryoprecipitate, and platelet transfusion (1:1:1 protocol in trauma)

7. Factor Deficiencies Affecting the Intrinsic Pathway

• Hemophilia A or B + concurrent ITP or bone marrow failure
• Less common; usually context makes it clear

Diagnostic Approach

Prolonged aPTT + Low Platelets
        |
        ├─ Check PT, fibrinogen, D-dimer
        |       ├─ All abnormal → DIC
        |       └─ Normal PT → consider APS, HIT, liver disease
        |
        ├─ Mixing study
        |       ├─ Corrects → factor deficiency
        |       └─ Does NOT correct → inhibitor (lupus anticoagulant, factor inhibitor)
        |
        ├─ On heparin? → Check anti-PF4 antibody (4T score for HIT)
        |
        ├─ Schistocytes on smear? → TTP / HUS
        |
        └─ Chronic liver disease? → LFTs, imaging

Quick Reference Table

Causes of Increased INR (Prolonged PT)

Major Categories

1. Liver Disease

• Mechanism: Hepatocytes synthesize all coagulation factors; hepatocellular dysfunction reduces factor production
• Seen in: hepatitis (acute/chronic), cirrhosis, acute liver failure, fatty liver disease
• PT prolonged >5 s above control that does not correct with parenteral vitamin K = poor prognostic sign in acute hepatitis
• INR is a component of the MELD score (along with bilirubin and creatinine) — used to assess severity of hepatic decompensation and liver transplant allocation
• (Harrison's, p. 9331)

2. Vitamin K Deficiency

• Mechanism: Factors II, VII, IX, X require vitamin K for gamma-carboxylation (activation)
• Causes:
  • Malabsorption: fat malabsorption (Crohn's, celiac disease, short bowel syndrome)
  • Cholestasis / Obstructive jaundice: bile salts needed for vitamin K (fat-soluble) absorption
  • Poor dietary intake (prolonged fasting, malnutrition, ICU patients on antibiotics)
  • Broad-spectrum antibiotics eliminating gut flora (which produce vitamin K2)
  • Neonates (physiologic vitamin K deficiency → hemorrhagic disease of the newborn)
• Key test: INR corrects after IV/SC vitamin K administration → confirms deficiency
• (Evaluation of Abnormal Liver Chemistries, p. 4)

3. Anticoagulant Therapy

4. Disseminated Intravascular Coagulation (DIC)

• Consumptive coagulopathy → depletion of multiple clotting factors
• Both PT and aPTT prolonged
• Low fibrinogen, low platelets, elevated D-dimer
• Triggered by sepsis, trauma, malignancy, obstetric emergencies

5. Factor Deficiencies (Inherited or Acquired)

• Factor VII deficiency: isolated PT prolongation (aPTT normal) — factor VII has the shortest half-life (~4–6 hours)
• Factor V deficiency: both PT and aPTT prolonged
• Acquired inhibitors against specific factors (rare)

6. Hypothermia

• Enzymatic activity of clotting factors is temperature-dependent
• Core temperature <35°C impairs coagulation cascade
• Common in major trauma (lethal triad: hypothermia + acidosis + coagulopathy)
• (Evaluation of Abnormal Liver Chemistries, p. 4)

7. Other Causes

• Massive transfusion — dilutional coagulopathy
• Amyloidosis — factor X adsorption onto amyloid fibrils
• Antiphospholipid syndrome — occasionally prolongs PT
• Disseminated malignancy

Diagnostic Algorithm

Elevated INR
      |
      ├─ On warfarin / heparin? → Drug effect (therapeutic or supratherapeutic)
      |
      ├─ Correct with Vitamin K?
      |       ├─ YES → Vitamin K deficiency (malabsorption, cholestasis, dietary)
      |       └─ NO → Liver disease (hepatocellular dysfunction) or inhibitor
      |
      ├─ Check aPTT
      |       ├─ aPTT also prolonged → Common pathway defect, DIC, liver disease
      |       └─ aPTT normal → Factor VII deficiency (isolated), early warfarin
      |
      ├─ Fibrinogen ↓ + D-dimer ↑ + Platelets ↓ → DIC
      |
      └─ Liver function tests → Hepatocellular vs. cholestatic pattern

Quick Reference Table

B-Lines on Lung Ultrasound

What Are B-Lines?

Defining Features

Normal lung: shows horizontal A-lines (reverberation artifacts) — absence of B-lines. ≥3 B-lines in a single intercostal space = interstitial syndrome (pathological)

Mechanism

Causes Based on B-Line Pattern

Clinical Conditions Causing B-Lines

Cardiac / Cardiogenic

• Acute decompensated heart failure (most common) — bilateral, symmetric, diffuse B-lines
• Cardiogenic pulmonary edema
• Fluid overload

Pulmonary / Non-Cardiogenic

• Pneumonia — focal, unilateral, asymmetric B-lines
• ARDS — bilateral but heterogeneous/patchy distribution
• Interstitial lung disease (ILD/UIP/NSIP) — bilateral, predominantly basal, chronic
• Pulmonary contusion — post-trauma, focal
• COVID-19 pneumonitis — bilateral, patchy

Other

• Pleural disease — subpleural consolidation
• Post-radiotherapy fibrosis — localized

B-Lines: Cardiogenic vs. Non-Cardiogenic Differentiation

BLUE Protocol (Bedside Lung Ultrasound in Emergency)

Dyspnea / Respiratory failure
          |
    Anterior zones bilateral
          |
     B-lines present?
     /            \
   YES              NO (A-lines)
   |                    |
Pulmonary edema     Check DVT / PE
(heart failure)     or COPD / asthma
          |
  Focal B-lines / consolidation?
          → Pneumonia

Key Clinical Pearls

• B-lines are dynamic — they decrease with diuresis in heart failure (useful for monitoring treatment response)
• Bilateral diffuse B-lines + reduced LV function on cardiac echo = cardiogenic pulmonary edema until proven otherwise
• B-lines cannot distinguish all causes alone — always correlate with clinical history, cardiac echo (EF, E/e'), and other zones
• Absence of B-lines with presence of A-lines + absent lung sliding = pneumothorax