Deciding Whether to Start Acitrom (Acenocoumarol) in RHD

Step 1: Confirm a Clear Indication

Key point from Goldman-Cecil Medicine: "Because patients with concomitant mitral stenosis and atrial fibrillation have an extraordinarily high risk for systemic embolism, they should undergo chronic anticoagulation with warfarin at an INR target of 2.5 to 3.5 unless there is a serious contraindication... Atrial fibrillation with rheumatic mitral stenosis or a mechanical heart valve requires VKA anticoagulation instead of direct-acting oral anticoagulants (DOACs)." - Goldman-Cecil Medicine

Step 2: Assess Contraindications (When NOT to Start)

• Active bleeding (GI, intracranial, etc.)
• Recent hemorrhagic stroke or intracranial bleed
• Pregnancy (especially first trimester and near term - fetal warfarin syndrome risk)
• Severe thrombocytopenia (platelets <50,000)
• Known bleeding disorders (hemophilia, severe liver failure with coagulopathy)

• Recent major surgery or trauma
• Uncontrolled hypertension (BP >180/110 mmHg)
• Active peptic ulcer disease
• Heavy alcohol use or poor compliance
• Inability to monitor INR (no access to lab)
• Falls risk in elderly

Step 3: Confirm Patient Suitability (Practical Checklist)

1. Indication confirmed - AF, prior embolism, mechanical valve, large LA with spontaneous echo contrast?
2. Baseline investigations done - CBC, liver function tests, renal function, baseline INR/PT, baseline ECG and echo
3. INR monitoring is feasible - Patient lives near a lab, can come for regular INR checks (initially weekly until stable, then monthly)
4. Interacting drugs identified - Many drugs alter Acitrom metabolism (NSAIDs increase bleeding risk; antibiotics, antifungals, amiodarone potentiate it; rifampicin reduces it)
5. Dietary consistency - Patient counselled about consistent vitamin K intake (green leafy vegetables affect INR)
6. Patient counselled about bleeding signs and when to seek emergency care
7. No active bleeding source (check for history of GI bleed, haematuria, epistaxis)

Important Note: RHD in Sinus Rhythm Without AF

• Mild-to-moderate mitral stenosis in sinus rhythm without prior embolism or LA thrombus - Acitrom is generally NOT routinely indicated
• Anticoagulation in this scenario remains controversial and is individualized based on echo findings (LA size, spontaneous contrast)

Summary Decision Algorithm

RHD Patient
    |
    ├─ Has AF / Prior embolism / Mechanical valve?
    │       YES → Acitrom INDICATED (mandatory VKA, not DOAC)
    │
    ├─ Sinus rhythm + Large LA (>55mm) or spontaneous echo contrast?
    │       YES → Acitrom REASONABLE (Class IIa)
    │
    ├─ Sinus rhythm + No above risk factors?
    │       → Acitrom NOT routinely indicated
    |
    └─ Any indication present?
            Check contraindications → If none, confirm INR monitoring feasibility → Start Acitrom

Tuberculous Meningitis (TBM) - Complete Clinical Guide

1. Clinical Presentation

• Headache (>50% of cases), low-grade fever, malaise, anorexia for days to weeks
• Neck rigidity / meningism (75% of cases), Kernig's and Brudzinski's signs
• Lethargy, confusion, altered sensorium

• Cranial nerve palsies - especially ocular (CN III, IV, VI) due to basal exudate (20% of cases)
• Symptoms >5 days before presentation
• History of TB exposure or contact, prior TB, or immunocompromise (HIV)
• Evidence of TB elsewhere - pulmonary TB on CXR in ~2/3 of cases
• Systemic TB features: weight loss, night sweats, prolonged cough >2 weeks

2. Diagnosis

Uniform Case Scoring System (Marais Criteria)

• Definite TBM: AFB on CSF smear, positive CSF culture, or positive Xpert MTB/RIF + suggestive clinical features
• Probable TBM: Score ≥12 (if neuroimaging available) or ≥10 (if no neuroimaging). At least 2 points must come from CSF or imaging criteria
• Possible TBM: Score 6-11 (imaging available) or 6-9 (no imaging); alternative diagnosis not confirmed

CSF Analysis (Lumbar Puncture - cornerstone of diagnosis)

Harrison's 22e: "AFBs are infrequently seen on direct smear of CSF sediment, but repeated lumbar punctures increase the yield. Culture is diagnostic in up to 80% and remains the gold standard. Xpert MTB/RIF has sensitivity up to 80% and is the preferred initial option. A negative result does NOT exclude TBM."

Neuroimaging

• Basal meningeal enhancement (most characteristic)
• Hydrocephalus (communicating, due to obstruction of basal cisterns)
• Infarcts (from vasculitis of perforating arteries)
• Tuberculomas (ring-enhancing lesions)

Other Investigations

• CXR - look for pulmonary TB, miliary pattern
• Mantoux / TST - helpful if positive, but negative in immunocompromised
• IGRA (Interferon-gamma release assay) - QuantiFERON
• Sputum AFB / GeneXpert if pulmonary involvement suspected
• HIV serology - mandatory in all TBM cases
• Blood: CBC, LFT, RFT, electrolytes (hyponatremia from SIADH is common)
• Fundoscopy - papilledema, choroidal tubercles

3. Treatment

ATT Regimen

• Isoniazid (H/INH): 5 mg/kg/day (max 300 mg) - best CNS penetration
• Rifampicin (R/RIF): 10 mg/kg/day (max 600 mg)
• Pyrazinamide (Z/PZA): 20-35 mg/kg/day
• Ethambutol (E/EMB): 15 mg/kg/day

Note: Ethambutol and ethionamide have poor CSF penetration once inflammation resolves. Fluoroquinolones (levofloxacin/moxifloxacin) have excellent CNS penetration and are useful in MDR-TBM as fourth drugs.

Adjunctive Corticosteroids (MANDATORY)

Harrison's 22e: "Clinical trials demonstrated that patients given adjunctive glucocorticoids experience faster resolution of CSF abnormalities and elevated CSF pressure, resulting in lower rates of death or severe disability and relapse. Dexamethasone significantly enhanced survival among persons >14 years."

Note on HIV patients: A recent placebo-controlled trial showed no benefit from adjunctive dexamethasone in TBM patients with HIV - individualise this decision.

4. Complications and Monitoring

Common Complications

Monitoring During Treatment

1. Serial LPs - monitor CSF cell count, protein, glucose response
2. Serial neuroimaging (especially if tuberculoma present - may initially enlarge before resolving)
3. LFTs monthly - INH and RIF are hepatotoxic; stop ATT if symptomatic hepatitis or ALT >3x ULN with symptoms
4. Visual acuity and color vision - Ethambutol can cause optic neuropathy (check monthly)
5. Serum sodium - watch for SIADH
6. GCS / neurological status - daily in acute phase
7. Uric acid - Pyrazinamide causes hyperuricemia

5. Prognosis

• Overall mortality: ~10-20% in treated cases; up to ~50% when treatment is delayed to the coma stage
• Neurological sequelae in 20-30% of survivors: cognitive impairment, seizures, hemiparesis, visual defects, deafness
• HIV co-infection worsens prognosis significantly (mortality ~21% or higher)
• Key message: Early diagnosis and immediate ATT initiation is the single most important determinant of outcome

Summary - Immediate Action in Suspected TBM

Suspected TBM
    ↓
1. Urgent CT/MRI head (rule out mass lesion before LP)
2. Lumbar puncture → CSF for: cells, protein, glucose, AFB smear, culture, Xpert MTB/RIF, ADA
3. CXR, HIV test, LFT, RFT, electrolytes, CBC
4. Start ATT IMMEDIATELY (do not wait for culture)
    → 2HRZE / 7-10HR
5. Add Dexamethasone (taper over 6-8 weeks)
6. Pyridoxine 50mg/day with INH
7. Monitor for hyponatremia, raised ICP, seizures
8. Neurosurgery consult if hydrocephalus develops