When to intubate in GCS?

GCS ≤ 8 requires intubation for airway protection. The patient cannot protect their own airway at this level of consciousness. Motor score is the most prognostically important component.

What is the best initial fluid for sepsis resuscitation?

Lactated Ringer's (LR) is the preferred resuscitation fluid. The SMART trial (2018) showed balanced crystalloids reduced death, new renal failure, and persistent renal dysfunction compared to normal saline.

When to start vasopressors in septic shock?

Start norepinephrine (first-line vasopressor) if MAP remains < 65 mmHg after initial 30 mL/kg crystalloid resuscitation, or earlier if patient is profoundly hypotensive. Do not delay pressors to complete full fluid resuscitation.

Why can serum uric acid be normal during acute gout?

During acute inflammation, IL-6 increases renal urate excretion and redistributes urate from plasma to tissues. Up to 40% of acute gout flares have normal serum uric acid. Joint aspiration with polarized microscopy is needed for definitive diagnosis.

How do you distinguish lupus flare from infection in SLE?

Key clues: CRP is low/normal in flare but elevated in infection. Complement (C3/C4) drops in flare but is normal/elevated in infection. Procalcitonin is elevated in bacterial infection but normal in flare. Anti-dsDNA rises in flare, stable in infection.

What is the difference between DKA and HHS?

DKA features acidosis (pH 600), hyperosmolality (> 320), and minimal ketosis -typically in Type 2 DM. DKA requires insulin drip; HHS requires aggressive fluid resuscitation first.

When to give tPA in acute ischemic stroke?

IV alteplase (tPA) can be given within 4.5 hours of last known well time in eligible patients. CT head must rule out hemorrhage first. For large vessel occlusion, mechanical thrombectomy can be performed up to 24 hours with favorable imaging.

What antibiotics for community-acquired pneumonia?

Inpatient non-ICU: ceftriaxone + azithromycin. ICU: ceftriaxone + azithromycin (add vancomycin if MRSA risk). Outpatient healthy: amoxicillin. Outpatient with comorbidities: augmentin + azithromycin or respiratory fluoroquinolone. Duration: 5 days if clinically stable for 48 hours.

How to interpret iron studies?

Iron deficiency: low ferritin (< 30), high TIBC, low iron, low transferrin saturation (< 20%). Anemia of chronic disease: normal/high ferritin (acute phase reactant), low TIBC, low iron. A ferritin of 50-100 in an inflamed patient may still represent iron deficiency.

What is the correction rate for hyponatremia?

Correct sodium no more than 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome (ODS). For symptomatic severe hyponatremia with seizures, give 3% hypertonic saline 100-150 mL bolus over 10-20 minutes. If overcorrected, use D5W + DDAVP rescue protocol.

When to start antibiotics in meningitis?

Within 30-60 minutes. Do NOT delay antibiotics for LP or CT. Draw blood cultures, start empiric antibiotics (vancomycin + ceftriaxone ± ampicillin if > 50 or immunocompromised), then perform LP when possible. Dexamethasone should be given before or with the first antibiotic dose.

DOACs vs warfarin in antiphospholipid syndrome?

DOACs are contraindicated in APS. The TRAPS trial (2018) showed rivaroxaban was inferior to warfarin with more thrombotic events in triple-positive APS patients. Warfarin with INR target 2-3 is the standard for APS, indefinitely.

How to manage scleroderma renal crisis?

ACE inhibitors (captopril) are life-saving -start immediately and titrate aggressively. Do NOT hold for rising creatinine. Steroids > 15 mg prednisone per day precipitate scleroderma renal crisis. ARBs are NOT a substitute -evidence is only for ACEi.

What are the 4 pillars of heart failure treatment?

Guideline-directed medical therapy (GDMT) for HFrEF: (1) ARNI or ACEi/ARB, (2) beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), (3) MRA (spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). All four should be initiated and titrated to target doses.

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HematologyCore

VTE Prophylaxis & Treatment

Every hospitalized patient needs VTE risk assessment. DVT and PE are preventable causes of inpatient death -know when to prophylax, how to diagnose, and how to treat.

🔍 Overview

VTE Spectrum

Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). PE is a DVT that has embolized to the pulmonary vasculature. ~600,000 VTE events/year in the US; ~100,000 deaths/year. Hospital-acquired VTE is the #1 preventable cause of hospital death.

Virchow's Triad

Stasis: Immobility, hospitalization, long flights, paralysis, obesity
Endothelial injury: Surgery, trauma, central lines, prior DVT, vasculitis
Hypercoagulability: Cancer (#1 acquired), pregnancy, OCP/HRT, Factor V Leiden, prothrombin mutation, antiphospholipid syndrome, nephrotic syndrome

Padua Prediction Score (VTE Prophylaxis)

Risk Factor	Points
Active cancer	3
Previous VTE (excluding SVT)	3
Reduced mobility (≥ 3 days)	3
Known thrombophilia	3
Recent (≤ 1 month) surgery or trauma	2
Age ≥ 70	1
Heart or respiratory failure	1
Acute MI or stroke	1
Acute infection or rheumatic disorder	1
Obesity (BMI ≥ 30)	1
Ongoing hormonal treatment	1

Padua ≥ 4 = High risk → pharmacologic prophylaxis. Padua < 4 = Low risk → ambulation + SCDs only. Also assess bleeding risk (IMPROVE score) before starting anticoagulation prophylaxis.

Key Facts

~50% of hospital DVTs are asymptomatic. Prophylaxis prevents them before they embolize.
Post-thrombotic syndrome: 20-50% of DVT patients develop chronic venous insufficiency (pain, swelling, ulcers)
Chronic thromboembolic pulmonary hypertension (CTEPH): ~4% of PE patients. Screen if persistent dyspnea after PE treatment.
Cancer-associated VTE: 4-7x increased risk. Consider occult cancer workup in unprovoked VTE (age-appropriate screening).

📋 On Rounds

Pimp Questions

What is the Padua Prediction Score and when do you give pharmacologic VTE prophylaxis?

Padua score stratifies VTE risk in medical patients. Score >= 4 = high risk, start pharmacologic prophylaxis (enoxaparin 40 mg SQ daily or heparin 5000 units SQ q8h). Score < 4 = low risk, ambulation + SCDs only. Key high-point items: active cancer (3), prior VTE (3), reduced mobility >= 3 days (3), known thrombophilia (3). Also assess bleeding risk (IMPROVE score) before anticoagulation.

What is the difference between the Wells score for DVT and the Wells score for PE?

Two separate scoring systems. DVT Wells: max ~9 points, score >= 2 = DVT likely (go to US), < 2 = unlikely (D-dimer first). PE Wells: max ~12.5 points, score > 4 = PE likely (CTPA directly), <= 4 = unlikely (D-dimer first). Key difference: PE Wells heavily weights clinical suspicion (PE most likely dx = 3 pts) and DVT signs (3 pts). Both use '-2' for alternative diagnosis. Never combine them.

When can you use the PERC rule to rule out PE without a D-dimer?

PERC applies ONLY to LOW pre-test probability patients. All 8 criteria must be negative: age < 50, HR < 100, SpO2 >= 95%, no hemoptysis, no estrogen use, no prior DVT/PE, no unilateral leg swelling, no surgery/trauma in 4 weeks. If all 8 negative, PE is ruled out without D-dimer (miss rate < 2%). Do NOT apply PERC to moderate or high pre-test probability patients. Kline et al., 2004

What is the age-adjusted D-dimer cutoff and why is it important?

For patients > 50 years old, the D-dimer cutoff = age x 10 ng/mL (e.g., 65-year-old = 650 instead of 500). D-dimer specificity decreases with age, leading to excessive CTPAs in elderly patients. The ADJUST-PE trial showed age-adjusted cutoffs increased specificity from 34% to 46% without missing any PEs, reducing unnecessary CTPAs by ~12%. Only use in PE-unlikely patients (Wells <= 4). ADJUST-PE, 2014

A patient with cancer develops a DVT. What anticoagulant do you use and why?

For cancer-associated VTE, LMWH (enoxaparin) was the historical standard based on the CLOT trial (52% recurrence reduction vs warfarin). Now DOACs (edoxaban per HOKUSAI-VTE Cancer, rivaroxaban per SELECT-D) are alternatives with similar efficacy and convenience. EXCEPTION: avoid DOACs in GI or GU cancers due to significantly higher mucosal bleeding risk. Warfarin is avoided in cancer (drug interactions, unreliable INR, inferior outcomes). Duration: as long as cancer is active. CLOT, 2003

When do you give tPA for PE and when do you NOT?

tPA (alteplase 100 mg IV over 2h) is indicated for MASSIVE PE only: sustained SBP < 90 for > 15 min, cardiac arrest, or persistent profound bradycardia. Do NOT give for submassive PE (RV strain + normal BP) - the PEITHO trial reduced hemodynamic collapse but increased intracranial hemorrhage (2.4%) and major bleeding (6.3%). Submassive PE = heparin + ICU monitoring + close observation for deterioration. PEITHO, 2014

How long do you anticoagulate after a first VTE?

Provoked by major transient risk (surgery, immobilization): 3 months. Provoked by minor risk (travel, estrogen): 3 months, consider extending. Unprovoked: minimum 3 months, then reassess - often extended indefinitely if low bleeding risk. Recurrent unprovoked: indefinite. Cancer-associated: as long as cancer is active. D-dimer after stopping anticoagulation helps guide (PROLONG study - elevated D-dimer after stopping = high recurrence risk, restart). PROLONG, 2006

What is HIT and how do you manage it?

Heparin-induced thrombocytopenia: immune-mediated platelet activation via PF4-heparin antibodies. Suspect when platelets drop > 50% from baseline on days 5-14 of heparin exposure. Use 4T score to risk-stratify. Management: STOP ALL heparin immediately (including flushes and line locks). Start a non-heparin anticoagulant (argatroban if hepatic function okay, bivalirudin if renal failure). Send PF4 antibody + SRA. Do NOT give warfarin until platelets > 150K (risk of venous limb gangrene).

Why is apixaban preferred over warfarin for most non-cancer VTE?

The AMPLIFY trial showed apixaban was non-inferior to warfarin for preventing recurrent VTE (2.3% vs 2.7%) with 56% less major bleeding (0.6% vs 1.8%). Advantages over warfarin: no heparin bridge needed (load 10 mg BID x 7 days then 5 mg BID), no INR monitoring, fewer drug-food interactions, predictable pharmacokinetics, rapid onset. Disadvantages: cost, limited reversal agents (andexanet alfa), less data in severe renal failure or mechanical valves. AMPLIFY, 2013

Q: What is the Wells Score for PE?

A: Clinical signs of DVT (3), PE most likely dx (3), HR > 100 (1.5), immobilization/surgery in 4 wks (1.5), prior DVT/PE (1.5), hemoptysis (1), cancer (1). Score > 4 = PE likely → CTPA. Score ≤ 4 = PE unlikely → D-dimer first. Simplifies to 2-tier: likely vs unlikely.

Q: When can you use PERC to rule out PE?

A: Only in LOW pre-test probability patients. All 8 must be negative: age < 50, HR < 100, O2 sat ≥ 95%, no hemoptysis, no estrogen use, no prior DVT/PE, no unilateral leg swelling, no surgery/trauma in 4 weeks. If ALL negative → PE ruled out without D-dimer. Misses < 2%.

Q: What is the age-adjusted D-dimer cutoff?

A: For patients > 50: cutoff = age × 10 (e.g., 65yo → cutoff 650 ng/mL instead of 500). Validated in ADJUST-PE trial -increased specificity from 34% to 46% without missing PEs. Only use in PE-unlikely patients. Reduces unnecessary CTPAs by ~12%.

Q: What anticoagulant do you use for cancer-associated VTE?

A: LMWH was standard (CLOT trial). Now DOACs (edoxaban per HOKUSAI-VTE Cancer, rivaroxaban per SELECT-D) are alternatives EXCEPT in GI/GU cancers (higher bleeding risk with DOACs). Avoid warfarin in cancer -harder to manage, drug interactions, unreliable INR.

Q: When do you give tPA for PE?

A: Massive PE only: sustained hypotension (SBP < 90 for > 15 min), pulselessness, or persistent bradycardia. Alteplase 100mg IV over 2h is standard. NOT for submassive PE (RV strain + normal BP) -PEITHO trial showed tPA reduced hemodynamic collapse but increased ICH. Submassive = anticoagulation + close monitoring.

Q: How long do you anticoagulate after a first VTE?

A: Provoked (surgery, immobility): 3 months. Unprovoked: minimum 3 months, then reassess -often extended/indefinite if low bleeding risk. Cancer: treat as long as cancer is active. Recurrent unprovoked: indefinite. Use D-dimer after stopping to guide (PROLONG study).

Clinical Examples

Case 1: DVT -Provoked

58M, 5 days post-TKR, left calf swelling and tenderness. D-dimer 2400. Duplex US: acute occlusive thrombus in left popliteal vein. Dx: Provoked proximal DVT. Start enoxaparin (Lovenox) 1mg/kg BID, bridge to apixaban (Eliquis). Duration: 3 months (provoked by surgery).

Case 2: Submassive PE

45F on OCPs presents with acute dyspnea, HR 115, BP 110/70, SpO2 91%. CTPA: bilateral PE with RV/LV ratio > 1. Troponin 0.15. BNP 450. Dx: Submassive PE (RV strain + elevated biomarkers, but hemodynamically stable). Start heparin drip. Monitor closely in ICU. tPA NOT indicated unless hemodynamic decompensation. PEITHO, 2014

Case 3: Cancer-Associated VTE

62F with metastatic pancreatic cancer, found to have incidental PE on staging CT. Asymptomatic, hemodynamically stable. Dx: Cancer-associated VTE. Start enoxaparin (Lovenox) 1mg/kg BID (preferred over DOAC in GI malignancy due to bleeding risk). CLOT, 2003 Duration: as long as cancer is active or on treatment.

Case 4: HIT with DVT

70M on heparin drip for DVT, day 7. Platelets dropped from 220K to 85K (60% decline). 4T score: 6 (high probability). Dx: HIT. STOP all heparin immediately (including flushes). Start argatroban (direct thrombin inhibitor). Send PF4 antibody + SRA. Do NOT give warfarin until platelets > 150K (risk of warfarin-induced venous limb gangrene).

Sample Presentation

Mrs. Thompson is a 52-year-old woman presenting with 3 days of left leg swelling and pain. She returned from a 12-hour flight 5 days ago. No prior VTE. On estrogen HRT. Exam: left calf 3cm larger than right, pitting edema, tenderness along deep veins, positive Homan's sign. Wells DVT score: 3 (calf swelling > 3cm, pitting edema, entire leg swollen). D-dimer: 1,800 ng/mL.

Key Points: High pre-test probability DVT (Wells ≥ 2 + elevated D-dimer). Obtain duplex ultrasound to confirm. Risk factors: prolonged travel + estrogen. If proximal DVT confirmed, start anticoagulation (apixaban preferred for non-cancer VTE). Duration 3 months if provoked (travel + estrogen). Counsel to stop HRT. No thrombophilia workup needed for first provoked event.

Daily Rounds Checklist

VTE prophylaxis ordered? Check every patient, every day. Document reason if held.
Anticoagulation therapeutic? aPTT (heparin drip), anti-Xa (LMWH), INR (warfarin)
Platelet monitoring: q2-3 days on heparin (days 4-14) for HIT surveillance
Renal function: CrCl for LMWH/DOAC dosing adjustments
Bleeding assessment: GI symptoms, hematuria, gum bleeding, hemoptysis, surgical site
Leg symptoms: Swelling trending? Pain improving? Signs of extension?
Hemodynamics (PE): HR, BP, SpO2 trending. Any signs of RV failure?
Transition plan: Bridge to oral anticoagulation. Discharge with follow-up (hematology if unprovoked/recurrent)

🧪 Workup

DVT Diagnosis

Wells DVT Score	Points
Active cancer (treatment within 6 months)	1
Paralysis/paresis/recent cast of lower extremity	1
Bedridden > 3 days or major surgery within 12 weeks	1
Localized tenderness along deep venous system	1
Entire leg swollen	1
Calf swelling > 3 cm compared to other leg	1
Pitting edema (greater in symptomatic leg)	1
Collateral superficial veins (non-varicose)	1
Previously documented DVT	1
Alternative diagnosis as likely or more likely	-2

Score ≥ 2: DVT likely → duplex ultrasound. Score < 2: DVT unlikely → D-dimer first (if negative, DVT ruled out).

PE Diagnosis

Wells PE Score	Points
Clinical signs/symptoms of DVT	3
PE is #1 diagnosis (or equally likely)	3
Heart rate > 100	1.5
Immobilization (≥ 3 days) or surgery in prior 4 weeks	1.5
Previous DVT/PE	1.5
Hemoptysis	1
Malignancy (treatment in last 6 months or palliative)	1

Score > 4 (PE likely): → CTPA directly. Score ≤ 4 (PE unlikely): → D-dimer first. Use age-adjusted D-dimer (age × 10 for patients > 50) ADJUST-PE, 2014

PERC Rule (PE Rule-Out Criteria)

PERC: Use ONLY if pre-test probability is LOW. All 8 must be negative to rule out PE without D-dimer: Age < 50, HR < 100, SpO2 ≥ 95%, no hemoptysis, no estrogen, no prior DVT/PE, no unilateral leg swelling, no surgery/trauma in 4 weeks.

Imaging

Duplex ultrasound: First-line for DVT. Sensitivity 94%, specificity 98% for proximal DVT. Lower sensitivity for calf DVT (~70%).
CTPA: Gold standard for PE. Sensitivity 83-100%, specificity 89-97%. PIOPED II, 2006
V/Q scan: Alternative if CTPA contraindicated (contrast allergy, renal failure). Best when CXR is normal. Reports as normal/low/intermediate/high probability.
Bedside echo: RV dilation, RV hypokinesis, McConnell's sign (RV free wall akinesis with apical sparing). Useful in massive PE when too unstable for CTPA.

PE Risk Stratification

Category	Hemodynamics	RV Dysfunction	Biomarkers	Mortality	Treatment
Massive	SBP < 90 or arrest	Yes	Elevated	25-65%	tPA + heparin
Submassive	Normal	Yes	Elevated (troponin/BNP)	3-15%	Heparin + ICU monitoring
Low-risk	Normal	No	Normal	< 1%	Anticoagulation

💊 Treatment

VTE Prophylaxis

Agent	Dose	Notes
Enoxaparin (Lovenox)	40mg SQ daily	First-line medical prophylaxis. Adjust for CrCl < 30 (30mg daily). Hold if platelets < 50K or active bleeding.
Heparin (UFH)	5000 units SQ q8h	Use if CrCl < 30 or high bleeding risk (can reverse with protamine). TID dosing > BID for medical patients.
SCDs (mechanical)	Bilateral	Use alone if active bleeding, platelets < 50K, or high bleed risk. Use WITH pharmacologic in highest-risk patients. Remove for ambulation.
Fondaparinux (Arixtra)	2.5mg SQ daily	Alternative if HIT history. No platelet monitoring needed. Contraindicated CrCl < 30.

VTE prophylaxis is a quality measure. Every medical patient with Padua ≥ 4 and every surgical patient should have pharmacologic prophylaxis unless contraindicated. Document the reason if held (active bleeding, platelets < 50K, etc).

Acute Treatment

Agent	Dose	Monitoring	Notes
Heparin drip (UFH)	80 units/kg bolus → 18 units/kg/hr	aPTT q6h → q12h when stable	Use for massive PE, renal failure, high bleed risk (short half-life, reversible)
Enoxaparin (Lovenox)	1mg/kg SQ BID or 1.5mg/kg daily	Anti-Xa if obese or renal impairment	Preferred for most DVT. Avoid if CrCl < 30.
Apixaban (Eliquis)	10mg BID × 7 days → 5mg BID	None routinely	No heparin lead-in needed. First-line for non-cancer VTE. AMPLIFY, 2013
Rivaroxaban (Xarelto)	15mg BID × 21 days → 20mg daily	None routinely	No heparin lead-in. Once-daily maintenance. EINSTEIN-PE, 2012
Warfarin (Coumadin)	Target INR 2.0-3.0	INR daily → weekly → monthly	Requires 5-day heparin bridge. Cheap. Use if mechanical valve, APS, severe renal failure.
Edoxaban (Savaysa)	60mg daily (after 5-day heparin lead-in)	None routinely	Requires parenteral lead-in. Reduce to 30mg if CrCl 15-50 or weight ≤ 60kg. HOKUSAI-VTE, 2013

Duration of Anticoagulation

Scenario	Duration	Rationale
Provoked by major transient risk (surgery, immobilization)	3 months	Low recurrence risk once risk factor resolved (~3%/year)
Provoked by minor transient risk (travel, estrogen, minor injury)	3 months (consider extended)	Intermediate recurrence risk. Reassess at 3 months.
Unprovoked (first event)	≥ 3 months → reassess	15% recurrence at 2 years if stopped. Extend if low bleed risk. D-dimer after stopping helps guide (PROLONG).
Recurrent unprovoked	Indefinite	~30% recurrence if stopped. Benefit of continued anticoagulation outweighs bleeding risk.
Cancer-associated	As long as cancer active	LMWH or DOAC (not warfarin). Reassess every 3-6 months. CLOT, 2003

Special Situations

Cancer-associated VTE: LMWH or edoxaban/rivaroxaban (avoid DOACs in GI/GU cancers -bleeding). Avoid warfarin. Treat indefinitely while cancer active.
Pregnancy: LMWH only (enoxaparin 1mg/kg BID). Warfarin is teratogenic. DOACs contraindicated. Hold LMWH 24h before delivery.
Renal failure (CrCl < 30): UFH or dose-adjusted LMWH (enoxaparin 1mg/kg daily, monitor anti-Xa). Warfarin safe. Apixaban can be used (less renal clearance). Avoid rivaroxaban, edoxaban.
HIT: Stop ALL heparin. Start argatroban (hepatic metabolism, use in renal failure) or bivalirudin. Transition to warfarin only after platelets > 150K. Fondaparinux is an alternative.
Obesity (> 120kg or BMI > 40): Use weight-based LMWH with anti-Xa monitoring. DOACs may have reduced efficacy (limited data). Consider heparin drip for acute treatment.

DOAC Unified Comparison

DOAC	VTE dosing	Renal cutoffs	Reversal agent	Notes
Apixaban (Eliquis) PREFERRED non-cancer	10 mg BID × 7 d → 5 mg BID. Extended Rx: 2.5 mg BID after 6 mo.	Avoid CrCl < 25 (no dose data). Approved down to CrCl 15 by FDA but data weak.	Andexanet alfa (Andexxa) bolus + 2-h infusion. Alternative: 4F-PCC (Kcentra) 50 u/kg if andexanet unavailable.	Lowest major-bleed signal of any DOAC (AMPLIFY 0.6%). No food restriction. Twice-daily dosing the only downside.
Rivaroxaban (Xarelto)	15 mg BID × 21 d → 20 mg daily with food. Extended Rx: 10 mg daily after 6 mo.	Avoid CrCl < 30 for VTE.	Andexanet alfa · 4F-PCC 50 u/kg.	Once-daily after the 21-day load. Must take with food (absorption ↑ 39%). Slightly higher GI bleeding signal than apixaban.
Edoxaban (Savaysa)	60 mg daily AFTER 5-10 days of parenteral lead-in (heparin or LMWH). Reduce to 30 mg if CrCl 15-50, weight ≤ 60 kg, or strong P-gp inhibitor.	Avoid CrCl < 15.	Andexanet alfa (off-label) · 4F-PCC.	Used in HOKUSAI-VTE Cancer for cancer-associated VTE. Lead-in requirement makes it less convenient than apixaban/riva.
Dabigatran (Pradaxa)	150 mg BID AFTER 5-10 days of parenteral lead-in.	Avoid CrCl < 30.	Idarucizumab (Praxbind) 5 g IV -specific antidote, works within minutes.	Direct thrombin inhibitor (others are factor Xa). High GI bleeding signal at 150 mg dose. Best reversal of any DOAC. Dyspepsia common.

Anticoagulation Reversal -Major Bleeding

Major bleeding: intracranial hemorrhage, retroperitoneal bleed, hemodynamic compromise, transfusion ≥ 2 units, drop in Hgb ≥ 2 g/dL, or bleeding into a critical site. Stop the anticoagulant, apply local hemostasis, transfuse as needed, and reverse with the agent below.

Anticoagulant	Reversal	Dose / Notes
Warfarin	4F-PCC (Kcentra) + Vitamin K 10 mg IV	4F-PCC dose by INR: INR 2-4 → 25 u/kg; INR 4-6 → 35 u/kg; INR > 6 → 50 u/kg (max 5000 u). Faster and less volume than FFP. Always co-give Vitamin K 10 mg IV -PCC effect lasts ~6 h, Vit K provides durable reversal. FFP only if PCC unavailable (15-30 mL/kg).
Unfractionated heparin (UFH)	Protamine sulfate	1 mg per 100 units of heparin given in the last hour. Last 1-2 h → 0.5 mg per 100 u. Last 2-4 h → 0.25 mg per 100 u. Max 50 mg single dose. Watch for hypotension and anaphylaxis (especially in fish-allergy or prior protamine exposure -e.g., NPH insulin patients).
LMWH (enoxaparin)	Protamine -partial reversal only	Reverses ~60% of anti-Xa activity. Within 8 h of dose: 1 mg protamine per 1 mg enoxaparin. 8-12 h after dose: 0.5 mg per 1 mg. > 12 h: not effective. Consider 4F-PCC if life-threatening.
Apixaban / Rivaroxaban / Edoxaban (Factor Xa inhibitors)	Andexanet alfa (Andexxa) 1st-line · 4F-PCC alternative	Andexanet bolus + 2-h infusion (low-dose 400 mg + 4 mg/min, or high-dose 800 mg + 8 mg/min depending on agent / time / dose). Alternative: 4F-PCC 50 u/kg if andexanet unavailable, cost-prohibitive, or contraindicated. ANNEXA-4, 2019
Dabigatran (direct thrombin inhibitor)	Idarucizumab (Praxbind) 5 g IV -specific antidote	Two 2.5 g vials given consecutively over 5-10 min. Reversal within minutes (binds dabigatran 350× more tightly than thrombin). RE-VERSE AD, 2017. Hemodialysis is an alternative (60% removal in 2 h) -useful in advanced renal failure.
Argatroban / Bivalirudin (used in HIT)	No specific reversal	Stop infusion. Argatroban half-life ~50 min, bivalirudin ~25 min. Supportive care + transfusion. 4F-PCC may be considered if life-threatening but data limited.
Fondaparinux	No proven reversal	Stop the drug. Half-life 17-21 h. Recombinant factor VIIa has been tried (limited data, off-label). Consider 4F-PCC empirically. Hemodialysis ineffective.

Last-dose timing matters more than the lab number for DOACs. Specific anti-Xa or dabigatran levels are not routinely available; time since last dose drives the reversal decision. If the last dose was > 24-48 h ago in a patient with normal renal function, the drug is largely cleared and reversal may not be needed. Always confirm timing before reversing.

Thrombolysis & Catheter-Directed Therapy for PE

Massive PE (SBP < 90 × 15 min, cardiac arrest, or persistent bradycardia): Alteplase (tPA) 100 mg IV over 2 hours (or 50 mg bolus in arrest). Give WITH heparin. Absolute contraindications: active internal bleeding, recent (2 months) CVA, intracranial neoplasm. Mortality benefit outweighs bleed risk in massive PE.

Modality	Indication	Procedure	Evidence
Systemic tPA	Massive PE (hemodynamic compromise) only. NOT for submassive PE alone.	Alteplase 100 mg IV over 2 h, OR 50 mg bolus in cardiac arrest. Heparin co-administered.	PEITHO, 2014 -systemic lysis in submassive PE causes more harm than good.
Catheter-directed thrombolysis (CDT)	Intermediate-high-risk PE (submassive with RV strain) where systemic lysis is too risky; or massive PE with relative contraindication to systemic.	Catheter advanced into pulmonary artery; low-dose alteplase (1 mg/h × 12-24 h, total dose 10-24 mg) infused locally. EKOS adds ultrasound to fragment clot.	ULTIMA, 2014 · SEATTLE II, 2015
Mechanical thrombectomy (catheter aspiration)	Massive or intermediate-high-risk PE, especially when thrombolytics contraindicated. Increasingly used as first-line in submassive PE.	FlowTriever (Inari) -large-bore aspiration catheter; mechanical thrombus removal without lytic. Penumbra Indigo -aspiration. No tPA needed.	FLARE, 2019 · FLAME, 2023 · PEERLESS, 2024
Surgical embolectomy	Massive PE with absolute contraindication to all thrombolytics AND failed CDT/mechanical, OR clot-in-transit through PFO with paradoxical embolism risk.	Median sternotomy, cardiopulmonary bypass, direct extraction.	Largely superseded by catheter-based options. Reserved for centers with surgical expertise.
VA-ECMO	Cardiac arrest from PE or refractory shock as a bridge to definitive therapy (CDT, thrombectomy, or recovery).	Veno-arterial ECMO provides circulatory support while thrombus resolves or is removed.	Increasingly used at PERT-equipped centers. PERT consortium data supports multidisciplinary approach.

Activate PERT (Pulmonary Embolism Response Team) for any massive or intermediate-high-risk PE if your hospital has one. Cardiologists, IR, pulmonary, and CT surgery convene rapidly to choose between systemic lysis, CDT, mechanical thrombectomy, or surgical embolectomy. Time-to-decision matters as much as the choice.

HIT 4T Score

Category	2 points	1 point	0 points
Thrombocytopenia	Platelet drop > 50% AND nadir ≥ 20K	Drop 30-50% OR nadir 10-19K	Drop < 30% OR nadir < 10K
Timing	Days 5-10 (or < 1 day with prior heparin in last 30 d)	Possibly 5-10 (no clear records) or > 10 days	< 4 days without prior exposure
Thrombosis	New thrombosis · skin necrosis at injection site · acute systemic reaction after IV bolus	Progressive thrombosis · erythematous skin lesions · suspected (not confirmed) thrombosis	None
Other cause for thrombocytopenia	None apparent	Possible	Definite

Score 0-3 = low probability (HIT essentially excluded; PF4 antibody not needed). 4-5 = intermediate (send PF4 ELISA; stop heparin pending result). 6-8 = high (stop ALL heparin immediately, start non-heparin anticoagulant -argatroban or bivalirudin -before lab confirmation; send PF4 + serotonin release assay).

IVC Filter

Indication: Acute proximal DVT or PE with absolute contraindication to anticoagulation (active major bleeding, recent CNS surgery)
Retrievable filters preferred -remove once anticoagulation can be restarted (filter itself increases DVT risk)
NOT indicated as adjunct to anticoagulation in most cases

⚡ Summary

Summary

Prophylaxis

Padua ≥ 4 → enoxaparin 40mg SQ daily. CrCl < 30 → heparin 5000u SQ q8h. Bleeding risk → SCDs only.

DVT Workup

Wells DVT score. ≥ 2 → ultrasound. < 2 → D-dimer first. Negative D-dimer rules out DVT.

PE Workup

PERC (low risk only) → Wells PE. ≤ 4 → D-dimer (age-adjusted). > 4 → CTPA directly. PIOPED II gold standard.

First-Line Treatment

Apixaban 10mg BID × 7d → 5mg BID (non-cancer). LMWH for cancer VTE (avoid DOAC in GI cancers).

Duration

Provoked: 3 months. Unprovoked: ≥ 3 months → extend if low bleed risk. Cancer: indefinite. Recurrent: indefinite.

Pearl

HIT surveillance: platelets q2-3 days on heparin (days 4-14). > 50% drop → 4T score → PF4 antibody. Stop ALL heparin if suspected.

📄 One Pager

One-Pager

VTE Prophylaxis & Treatment

DVT/PE Management

Prophylaxis

Padua ≥ 4 → enoxaparin 40mg SQ daily. CrCl < 30 → heparin 5000u q8h. Active bleeding → SCDs only. EVERY patient needs VTE risk assessment on admission. Document if held.

Diagnosis Algorithm

DVT: Wells → if ≥ 2 → US; if < 2 → D-dimer. PE: PERC → Wells → if ≤ 4 → D-dimer (age-adjusted > 50); if > 4 → CTPA. Massive PE: bedside echo (RV dilation, McConnell's).

Acute Treatment

Non-cancer: apixaban 10mg BID × 7d → 5mg BID (no heparin lead-in). Cancer: LMWH (not DOAC in GI/GU). Massive PE: tPA 100mg/2h + heparin. HIT: stop heparin → argatroban.

Key Trials

AMPLIFY (apixaban) · EINSTEIN (rivaroxaban) · HOKUSAI-VTE (edoxaban) · CLOT (LMWH in cancer) · ADJUST-PE (age-adjusted D-dimer) · PEITHO (tPA in submassive PE -don't do it) · PIOPED II (CTPA).