11. Thromboembolism, Thromboprophylaxis

I. Thrombosis and Embolism: Basic Concepts

Thrombosis

Thrombosis: Formation of a blood clot inside a blood vessel during life
Clot can partially or completely occlude the vessel
Main mechanism → Virchow's triad

Endothelial injury → Surgery, trauma, inflammation, catheter, atherosclerosis
Stasis / disturbed flow → Immobility, heart failure, varicose veins, compression, long operation
Hypercoagulability → Malignancy, thrombophilia, pregnancy/puerperium, estrogen therapy, dehydration, sepsis

Risk Factors Important in Surgery

Age, obesity, smoking, previous VTE, family history of VTE
Cardiovascular disease, heart failure, stroke, varicose veins
Major abdominal/pelvic surgery, cancer surgery, orthopedic surgery, trauma
Long operation, general anesthesia, postoperative immobility, ICU stay
Malignant disease → Tumor procoagulants + inflammation + venous compression + chemotherapy
Inherited thrombophilia → Factor V Leiden, prothrombin mutation, antithrombin/protein C/protein S deficiency

Types of Thrombosis

Arterial thrombosis

Usually platelet-rich clot on atherosclerotic plaque or cardiac source
Consequences → Myocardial infarction, ischemic stroke, acute limb ischemia, mesenteric ischemia

Venous thrombosis

Usually fibrin/RBC-rich clot caused by stasis + hypercoagulability
DVT → Most important surgical VTE source; lower limb/pelvic veins → PE risk
Portal vein thrombosis → Cirrhosis, pancreatitis, intra-abdominal infection/malignancy → Portal hypertension
Budd-Chiari syndrome → Hepatic vein thrombosis → Abdominal pain, ascites, hepatomegaly
Renal vein thrombosis → Flank pain, hematuria, renal dysfunction; nephrotic syndrome risk

Embolism

Embolism: Blockage of a blood vessel by material that travels from another site
Thromboembolism: Thrombus forms → Detaches → Travels with blood flow → Lodges distally

Venous thromboembolism → DVT + pulmonary embolism
Arterial thromboembolism → Usually from heart/large arteries → Stroke, limb ischemia, organ infarction

Other Types of Embolism

Fat embolism → Long bone fracture, orthopedic surgery; respiratory distress + neurological signs + petechiae
Air/gas embolism → Central venous catheter, neurosurgery, diving/decompression
Septic embolism → Infected thrombus/vegetation → Abscesses, infarcts, sepsis
Amniotic fluid embolism → Obstetric emergency; hypoxia, shock, DIC
Tumor embolism → Malignancy invading vessels; rare but important

II. Venous Thromboembolism: DVT and PE

Deep Vein Thrombosis (DVT)

Clot formation in deep veins, most commonly lower limb/pelvic veins
Proximal DVT → Popliteal/femoral/iliac veins; higher PE risk
Distal DVT → Calf veins; lower PE risk but can propagate proximally

Symptoms / Signs

Unilateral calf/leg swelling, pain, tenderness
Warmth, erythema, superficial vein dilatation
Pitting edema, difference in calf circumference
Homan's sign is unreliable → Do not use alone to diagnose/exclude DVT
Can be asymptomatic, especially postoperative patients

Diagnosis

Assess clinical probability → Wells score / clinical risk estimate
D-dimer → Sensitive, non-specific; useful mainly in low-risk patients to exclude VTE
Duplex compression ultrasound → First-line test for suspected lower limb DVT
CT/MR venography → Selected pelvic/iliac thrombosis or unclear ultrasound
Contrast venography → Historical gold standard; rarely used now

Pulmonary Embolism (PE)

Occlusion of pulmonary artery/branches, usually by embolus from lower limb or pelvic DVT
Clinical danger → Increased pulmonary vascular resistance → RV strain/failure → Obstructive shock
Massive/high-risk PE → Hemodynamic instability, shock or cardiac arrest

Symptoms / Signs

Sudden dyspnea, pleuritic chest pain, tachypnea
Tachycardia, hypoxia, cough, hemoptysis
Syncope, hypotension, cyanosis, cardiac arrest in massive PE
Signs of DVT may be present but are often absent

Diagnosis

Initial assessment → ABCDE, oxygen saturation, BP, shock signs
Clinical probability → Wells / Geneva score; D-dimer only useful in low or intermediate probability
CT pulmonary angiography (CTPA) → First-line imaging in most stable patients
V/Q scan → Alternative if CTPA contraindicated, e.g. severe contrast allergy, renal failure, pregnancy context
ECG → Sinus tachycardia common; S1Q3T3 possible but not sensitive
Troponin/BNP → RV strain markers; help risk stratification
Echocardiography → RV dilatation/strain; important in unstable PE
Leg vein ultrasound → Can support diagnosis if DVT found and PE imaging difficult

III. Treatment of Thromboembolism

General Principles

Prevent clot extension and recurrence
Prevent fatal PE and post-thrombotic syndrome
Balance anticoagulation benefit against bleeding risk
Search for provoking factor → Surgery, cancer, immobility, thrombophilia, estrogen, infection

DVT / Stable PE Treatment

Anticoagulation is the main treatment if no contraindication
Options → LMWH, UFH, fondaparinux, DOACs, warfarin
DOACs often preferred for many non-pregnant, non-cancer or selected cancer patients if renal function and bleeding risk allow
LMWH useful in pregnancy, many cancer patients, early postoperative period, and when oral therapy is not suitable
UFH useful if severe renal failure, very high bleeding risk or likely urgent procedure → Short half-life, reversible
Warfarin requires overlap with parenteral anticoagulation until INR therapeutic

Massive / High-Risk PE

ABCDE resuscitation, oxygen, IV access, monitoring, ICU/PERT-type multidisciplinary decision if available
Anticoagulation with UFH often used because rapid adjustment/reversal is possible
Systemic thrombolysis → Indicated for PE with shock/persistent hypotension if bleeding risk acceptable
Catheter-directed thrombolysis/thrombectomy → If thrombolysis contraindicated or fails, depending on center
Surgical pulmonary embolectomy → Rare; selected massive PE when other methods unsuitable/failed

When Anticoagulation Is Contraindicated

Examples → Active major bleeding, recent high-risk intracranial surgery/bleed, severe uncontrolled coagulopathy
IVC filter → Consider only for acute VTE with absolute anticoagulation contraindication or recurrent PE despite adequate anticoagulation
Remove retrievable filter when anticoagulation becomes possible
Do not use IVC filter as routine prophylaxis

Complications

DVT → PE, recurrent VTE, post-thrombotic syndrome, chronic venous insufficiency
PE → Obstructive shock, sudden death, pulmonary infarction, chronic thromboembolic pulmonary hypertension
Anticoagulation → Bleeding, heparin-induced thrombocytopenia, drug interactions

IV. Thromboprophylaxis

Definition and Indications

Thromboprophylaxis: Measures to reduce VTE risk in high-risk patients
Basic rule → Assess VTE risk + bleeding risk for every surgical patient
Use mechanical methods when bleeding risk is high
Use pharmacological prophylaxis when VTE risk outweighs bleeding risk
Use combined mechanical + pharmacological prophylaxis in high VTE risk and acceptable bleeding risk

Common Indications

Major abdominal or pelvic surgery
Cancer surgery / active malignancy
Major orthopedic surgery → Hip/knee arthroplasty, hip fracture surgery
Trauma, spinal cord injury, ICU admission
Postoperative immobility, long operation, previous VTE, known thrombophilia
Immobilized medical patients → Stroke, heart failure, severe infection, respiratory failure

Mechanical Prophylaxis

Goal → Stimulate venous return → Prevent stasis
Early mobilization → Critical in all patients
Active/passive movement of extremities, ankle pump exercises
Graduated compression stockings / anti-embolism stockings
Intermittent pneumatic compression (IPC) → Often preferred mechanical device in hospital

Useful when anticoagulation contraindicated because of bleeding risk
Check contraindications → Severe peripheral arterial disease, severe leg edema/deformity, dermatitis/ulcer, acute limb ischemia
Must be fitted correctly; remove/check skin regularly

Pharmacological Prophylaxis / Anticoagulants

Drug group	Mechanism	Exam points
UFH Unfractionated heparin	Binds antithrombin → Inhibits thrombin (FIIa) and FXa	Short half-life; useful in renal failure/high bleeding risk; monitor aPTT if therapeutic dose; HIT risk
LMWH e.g. enoxaparin, dalteparin	Binds antithrombin → Mainly inhibits FXa	Common surgical prophylaxis; predictable effect; renal dose adjustment; lower HIT risk than UFH
Fondaparinux	Synthetic pentasaccharide → Antithrombin-mediated FXa inhibition	Not LMWH; avoid in severe renal failure; useful alternative in selected patients
Warfarin / coumarin	Inhibits vitamin K epoxide reductase → ↓ FII, VII, IX, X, protein C/S	Slow action; INR monitoring; many food/drug interactions; bridge needed for acute VTE start
DOACs	Dabigatran → Direct FIIa inhibitor Rivaroxaban/apixaban/edoxaban → Direct FXa inhibitors	No routine INR; renal function matters; used for VTE treatment and selected prophylaxis, especially orthopedic surgery

Timing and Duration

Start only after bleeding risk is acceptable and surgical hemostasis is secure
Typical start → Evening of surgery or within 6-12 h postoperatively depending on procedure/local protocol
If very high bleeding risk → Mechanical prophylaxis first, add anticoagulant later
General surgery → Continue until mobile/discharge; often 7-10 days depending on risk
Major orthopedic surgery → Extended prophylaxis; hip surgery often up to 28-35 days, knee often about 10-14 days or longer by protocol
Major abdominal/pelvic cancer surgery → Extended prophylaxis up to 4 weeks if bleeding risk acceptable

Bleeding Risk / Contraindications to Pharmacological Prophylaxis

Active bleeding or uncontrolled surgical bleeding
Severe thrombocytopenia or severe coagulopathy
Recent intracranial hemorrhage or high-risk neurosurgery
Severe uncontrolled hypertension
Planned neuraxial anesthesia/catheter → Strict timing rules with LMWH/DOACs
Severe renal failure → Avoid/adjust LMWH, fondaparinux and DOACs; consider UFH

Exam focus: Define thrombosis and embolism; explain Virchow's triad; classify arterial and venous thrombosis; know DVT and PE symptoms, diagnosis and treatment; describe mechanical and pharmacological thromboprophylaxis; mention timing, duration, bleeding risk, HIT, renal failure and IVC filter limitations.