HI THIS IS A PPT PRESENTATION ON VENOUS THROMBOEMBOLISM BASED ON HARRISONS 18TH EDITION. HOPE IT WILL HELP MY FELLOW COLLEAUGES.
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“If medicine is to fulfill her great task, then she must enter the political and social life. Do we not always find the diseases of the populace traceable to defects in society? In my listing, "CROWD DISEASES" or "ARTIFICIAL DISEASES" caused by poverty included typhus, scurvy, TB, leprosy, cholera, relapsing fever, and mental illness. If disease is an expression of individual life under unfavorable circumstances, then epidemics must be indicative of mass disturbances.” “Since disease so often results from poverty, the physicians are the natural attorneys of the poor, and the social problems should largely be solved by them. THE MEDICAL REFORM OF WHICH I often spoke WAS A REFORM OF SCIENCE AND SOCIETY. I urged that people treat criminal justice, education, unemployment, and occupational safety as if they are medical problems rather than political ones. Your era is beginning to do this.” “I have only one other suggestion for medical school teaching. Don't leave all mention of the social causes of disease to the social workers and statisticians. Lung cancer and emphysema are caused when ignorant children are lured into a deadly addiction. Endocarditis is caused by the cycle of poverty and lawlessness from which young people seek relief through IV drugs. Alcoholic cirrhosis is caused by frustrations that drive people to drink. Prematurity is caused by educational and economic barriers that prevent the poor from obtaining prenatal care. Urinary tract infections result when secretaries are forbidden to take unscheduled bathroom breaks, or when people are so accustomed to soda pop that they will not drink adequate water. Reasonable people can differ about solutions, but the underlying pathology is as much society's problem as it is the individual's.” RUDOLF VIRCHOW 13.10 1821 – 05.09.1902 1
Transcript
“If medicine is to fulfill her great task, then she must enter the political and social life. Do we not always find the diseases of the populace traceable to defects in society? In my listing, "CROWD DISEASES" or "ARTIFICIAL DISEASES" caused by poverty included typhus, scurvy, TB, leprosy, cholera, relapsing fever, and mental illness. If disease is an expression of individual life under unfavorable circumstances, then epidemics must be indicative of mass disturbances.”
“Since disease so often results from poverty, the physicians are the natural attorneys of the poor, and the social problems should largely be solved by them. THE MEDICAL REFORM OF WHICH I often spoke WAS A REFORM OF SCIENCE AND SOCIETY. I urged that people treat criminal justice, education, unemployment, and occupational safety as if they are medical problems rather than political ones. Your era is beginning to do this.”
“I have only one other suggestion for medical school teaching. Don't leave all mention of the social causes of disease to the social workers and statisticians. Lung cancer and emphysema are caused when ignorant children are lured into a deadly addiction. Endocarditis is caused by the cycle of poverty and lawlessness from which young people seek relief through IV drugs. Alcoholic cirrhosis is caused by frustrations that drive people to drink. Prematurity is caused by educational and economic barriers that prevent the poor from obtaining prenatal care. Urinary tract infections result when secretaries are forbidden to take unscheduled bathroom breaks, or when people are so accustomed to soda pop that they will not drink adequate water. Reasonable people can differ about solutions, but the underlying pathology is as much society's problem as it is the individual's.”
RUDOLF VIRCHOW 13.10 1821 – 05.09.19021
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Dr.Sudhanshu Mishra
Co-Ordinator;Dr.R.A.Manghani
HOD Medicine I&B
VENOUS THROMBOEMBOLISM
Venous Thromboembolic Disease
Venous thrombosis - ~ 5 million pts yearly Most caused by inadequate prophylaxis in hospitalized
pts 10 % suffer pulmonary embolism ~ 500,000 ~ 1% of all hospitalized pts have PE Contributes to 6 % of all hospital deaths ~ 125,000 deaths annually from PE
3rd most common cardiovascular cause of death (MI, CVA)
Most deaths occur early – PREVENTION IS KEY!! Diagnosis of PE made in < 30% when
contributes to death; < 10% if incidental
Virchow’s Triad
FactorsContributing
toVenous Thrombosis
FactorsContributing
toVenous Thrombosis
Altered Blood Flow(Stasis)
Blood Coagulability
Vessel WallDamage
Risk Factors for DVT Stasis
Surgery, trauma, immobility, paresis
Increasing age Pregnancy and postpartum Heart or respiratory failure Obesity
Vessel Injury Previous DVT Smoking Varicose veins Central venous
catheterization
Hypercoagulability Increasing age Malignancy Cancer therapy Estrogen therapy
(OCP or HRT) Acute medical illness Inflammatory bowel disease Nephrotic syndrome Myeloproliferative disorders Paroxysmal nocturnal
hemoglobinuria Inherited or acquired
thrombophilia
Hereditary conditions associates with DVT and PE
Most of the hereditary factors for clotting disorders is due to certain SNPs with relatively high frequencies in the general population.
– Types• Factor V Leiden (G1691A)• Prothrombin G20210A
– Features• These prothrombotic SNPs are found in almost half of
all cases of idiopathic thromboembolism• high gene frequency• low disease expression
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APPROACH TO DVT History Physical examination Probability scoring Blood test Imaging study
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Symptoms For patients with DVT most common
history is a cramp in the lower calf that persists for several days and becomes more uncomfortable as time progresses.
For patients who have PE most common history is unexplained breathlessness.
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Clinical Signs of DVT Unilateral edema Leg tenderness Redness, hotness Bluish discoloration Absent or decrease pulse
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Surgical Emergencies Phlegmasia cerul
ea dolens
Leg is cyanotic from massive ileofemoral venous obstruction. The leg is usually markedly edematous, painful, and cyanotic. Petechiae are often present.
Phlegmasia alba dolens
Painful white inflammation was originally used to describe massive ileofemoral venous thrombosis and associated arterial spasm. The affected extremity is often pale with poor or even absent distal pulses
Physical examination• Homans' test :Dorsiflexion of foot elicits
pain in posterior calf. Warning: it must be noted that it is of little diagnostic value and is theoretically dangerous because of the possibility of dislodgement of loose clot.
• Pratt's sign: Squeezing of posterior calf elicits pain.
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Signs or symptoms observed in patients with thromboembolism
Study
Stein et al., % (n= 117)
Anderson et al., % (n= 131)
Pulmonary embolism
Dyspnea 73 77
Tachypnea 70 70
Chest pain 66 55
Cough 37 —
Tachycardia 30 43
Cyanosis 1 18
Hemoptysis 13 13
Wheezing 9 —
Hypotension — 10
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Signs or symptoms observed in patients with thromboembolism
Study
Stein et al., % (n= 117)
Anderson et al., % (n= 131)
Pulmonary
Embolism
Syncope — 10
Elevated jugular venous pulse
— 8
Temperature >38.5°C
7 —
S-3 gallop 3 5
Pleural friction rub
3 2
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Signs or symptoms observed in patients with thromboembolism
Study
Stein et al., % (n= 117)
Anderson et al., % (n= 131)
Deep vein thrombosis
Swelling 28 88*
Pain 26 56
Tenderness — 55
Warmth — 42
Redness — 34
Homan’s sign 4 13
Palpable cord — 6
(Wells Score) Clinical Parameter Score Score
Active cancer (treatment ongoing, or within 6 mo or palliative)
+1
Paralysis or recent plaster immobilization of the lower extremities
+1
Recently bedridden for >3 d or major surgery <4 wk
+1
Localized tenderness along the distribution of the deep venous system
+1
Calf swelling >3 cm compared with the asymptomatic leg
+1
Pitting edema (greater in the symptomatic leg)
+1
Previous DVT documented +1
Collateral superficial veins (nonvaricose) +1
Alternative diagnosis (as likely or greater than that of DVT)
-2
Total of Above Score
High probability >3
Moderate probability 1 or 2
Low probability <0
Wells Score
BLOOD TESTS D-Dimer ELISA :-
D-dimer antibodies account for their high sensitivity for venous thrombo embolism.
D-dimer level may be elevated in any medical condition where clots form. D-dimer level is elevated in trauma, recent surgery, hemorrhage, cancer, and sepsis.
The D-dimer assays have low specificity for DVT; therefore,
they should only be used to rule out DVT, not to confirm the diagnosis of DVT
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D-dimer results should be used as follows:
A negative D-dimer assay result rules out DVT in patients with low-to-moderate risk and a Wells DVT score less than 2.
All patients with a positive D-dimer assay result and all patients with a moderate-to-high risk of DVT (Wells DVT score >2) require a diagnostic study.
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Elevated Cardiac Biomarkers Serum troponin and plasma heart-type fatty acid–
binding protein levels increase because of RV microinfarction.
Myocardial stretch results in elevation of brain natriuretic peptide or NT-pro-brain natriuretic peptide.
Elevated cardiac biomarkers predict an increase in major complications and mortality from PE
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ECG Changes
S1 Q3 T3 Pattern
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T-wave inversion
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Rt. Ventricular Strain
CXR Findings A normal or nearly normal chest x-ray often occurs in
PE. Well-established abnormalities include focal oligemia
(Westermark's sign), a peripheral wedged-shaped density above the diaphragm (Hampton's hump), and an enlarged right descending pulmonary artery (Palla's sign).
The best-known indirect sign of PE on transthoracic echocardiography is McConnell's sign: hypokinesis of the RV free wall with normal motion of the RV apex.
Transesophageal echocardiography can identify saddle, right main, or left main PE.
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Noninvasive Imaging Modalities Venous UltrasonographyCriteria for Establishing the Diagnosis of Acute DVTLack of vein compressibility (principal criterion)Vein does not "wink" when gently compressed in cross-sectionFailure to appose walls of vein due to passive distention Direct Visualization of Thrombus Homogeneous and Low echogenicityAbnormal Doppler Flow Dynamics Normal response: calf compression augments Doppler flow signal and confirms vein patency proximal and distal to DopplerAbnormal response: flow blunted rather than augmented with calf compression
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Chest CT Computed tomography of the chest with intravenous
contrast is the principal imaging test for the diagnosis of PE.
Multidetector-row spiral CT acquires all chest images with 1 mm of resolution during a short breath hold. This generation of CT scanners can image small peripheral emboli.
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Spiral CT
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Before
After
Lung Scanning Lung scanning has become a second-line diagnostic test
for PE, used mostly for patients who cannot tolerate intravenous contrast.
Small particulate aggregates of albumin labeled with a gamma-emitting radionuclide are injected intravenously and are trapped in the pulmonary capillary bed.
The perfusion scan defect indicates absent or decreased blood flow, possibly due to PE. Ventilation scans, obtained with a radiolabeled inhaled gas such as xenon or krypton, improve the specificity of the perfusion scan.
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High-probability ventilation-perfusion
scan
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High-probability ventilation-perfusion scan
Magnetic Resonance (MR) Contrast-Enhanced
When ultrasound is equivocal, MR venography with gadolinium contrast is an excellent imaging modality to diagnose DVT. MR imaging should be considered for suspected VTE patients with renal insufficiency or contrast dye allergy.
MR pulmonary angiography may detect large proximal PE but is not reliable for smaller segmental and subsegmental PE.
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MRA with contrast
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MRA Real Time
Invasive Diagnostic Modalities
Pulmonary AngiographyChest CT with contrast has virtually replaced invasive pulmonary angiography as a diagnostic test. Invasive catheter-based diagnostic testing is reserved for patients with technically unsatisfactory chest CTs and those in whom an interventional procedure such as catheter-directed thrombolysis or embolectomy is planned. A definitive diagnosis of PE depends on visualization of an intraluminal filling defect in more than one projection. Secondary signs of PE include abrupt occlusion ("cut-off") of vessels, segmental oligemia or avascularity, a prolonged arterial phase with slow filling, and tortuous, tapering peripheral vessels. Contrast PhlebographyVenous ultrasonography has virtually replaced contrast phlebography as the diagnostic test for suspected DVT
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Pulmonary angiogram
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Pulmonary Angiogram
Management of DVT
Non-pharmacological These include lifestyle changes likeAvoid smoking Eating a healthy balanced diet Getting regular exercise and Maintaining a healthy weight or losing weight if patient obeseLeg Raising:This reduces the pressure in the calf veins
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Travelling Drink enough amount of water Avoid taking sleeping pills as it can cause immobility Perform simple leg exercises, such as regularly flexing
ankles Take occasional short walks when possible Wear elastic compression stockings
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ANTICOAGULANTS Anticoagulation is the foundation for successful
treatment of DVT and PE Immediately effective anticoagulation is initiated with a
parenteral drug: unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux.
Parenteral agents are continued as a transition or "bridge" to stable, long-term anticoagulation with Warfarin.Since it requires 5–7 days to achieve a therapeutic effect. During that period, one should overlap the parenteral and oral agents.
However, anticoagulants do not directly dissolve thrombus that already exists.
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Unfractionated Heparin MOA is by binding to and accelerating the activity of
antithrombin, thus preventing additional thrombus formation and permitting endogenous fibrinolytic mechanisms to lyse clot that already has formed.
UFH is dosed to achieve a target activated partial thromboplastin time (aPTT) that is 2–3 times the upper limit of the laboratory normal.
For UFH, a typical intravenous bolus is 5000–10,000 units followed by a continuous infusion of 1000–1500 U/h
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ADVANTAGE The major advantage of
UFH is its short half-life. This is especially useful if the patient may undergo an invasive procedure such as embolectomy
DISADVANTAGE Major disadvantage of UFH
is that achieving the target aPTT is empirical and may require repeated blood sampling and heparin dose adjustment every 4–6 hours.
Furthermore, patients are at risk of developing heparin-induced thrombocytopenia
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Low-Molecular-Weight Heparins These fragments of UFH exhibit less binding to plasma
proteins and endothelial cells and consequently have greater bioavailability, a more predictable dose response, and a longer half-life than does UFH.
No monitoring or dose adjustment is needed unless the patient is markedly obese or has chronic kidney disease.
2 commonly used LMWH preparations are enoxaparin and dalteparin.
Enoxaparin is approved as a bridge to warfarin for VTE. Dalteparin is also approved as monotherapy without
warfarin for symptomatic VTE patients with cancer in a dose of 200 U/kg once daily for 30 days, followed by 150 U/kg once daily for months 2–6.
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Fondaparinux Fondaparinux, an anti-Xa pentasaccharide, is administered
as a once-daily subcutaneous injection in a prefilled syringe to treat DVT and PE as a "bridge" to warfarin.
No laboratory monitoring is required. Patients weighing <50 kg receive 5 mg, patients weighing
50–100 kg receive 7.5 mg, and patients weighing >100 kg receive 10 mg.
Fondaparinux is synthesized in a laboratory and, unlike LMWH or UFH, is not derived from animal products
It does not cause heparin-induced thrombocytopenia. The dose must be adjusted downward for patients with
renal dysfunction because the kidneys metabolize the drug.
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Warfarin This vitamin K antagonist prevents carboxylation
activation of coagulation factors II, VII, IX, and X. The full effect of warfarin requires at least 5 days even if
the prothrombin time, used for monitoring, becomes elevated more rapidly.
If warfarin is initiated as monotherapy during an acute thrombotic illness, a paradoxical exacerbation of hypercoagulability can increase the likelihood of thrombosis rather than prevent it.
Overlapping UFH, LMWH, or fondaparinux with warfarin for at least 5 days can counteract the early procoagulant effect of unopposed warfarin.
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Warfarin Dosing In an average-size adult, warfarin usually is initiated in a dose of 5
mg. Doses of 7.5 or 10 mg can be used in obese or large-framed young patients who are otherwise healthy.
Patients who are malnourished or who have received prolonged courses of antibiotics are probably deficient in vitamin K and should receive smaller initial doses of warfarin, such as 2.5 mg.
The Prothrombin time is standardized by calculating the International normalized ratio (INR), which assesses the anticoagulant effect of warfarin (Chap. 58). The target INR is usually 2.5, with a range of 2.0–3.0.
The warfarin dose is titrated to achieve the target INR. Proper dosing is difficult because hundreds of drug-drug and drug-
food interactions affect warfarin metabolism. Variables such as increasing age and comorbidities such as
systemic illness reduce the required warfarin dose
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Novel Anticoagulants Novel oral anticoagulants are administered in a fixed
dose, establish effective anticoagulation within hours of administration, require no laboratory coagulation monitoring, and have few of the drug-drug or drug-food interactions that make warfarin so difficult to dose.
Rivaroxaban, a factor Xa inhibitor, and Dabigatran, a direct thrombin inhibitor, are approved in Canada and Europe for prevention of VTE after total hip and total knee replacement.
Because of these drugs' rapid onset of action and relatively short half-life compared with warfarin, "bridging" with a parenteral anticoagulant is not required.
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Complications of Anticoagulants The most serious adverse effect of anticoagulation is hemorrhage. For life-
threatening or intracranial hemorrhage due to heparin or LMWH, protamine sulfate can be administered.
Major bleeding from warfarin is best managed with prothrombin complex concentrate. With non-life threatening bleeding in a patient who can tolerate large volume, fresh-frozen plasma can be used. For minor bleeding or to manage an excessively high INR in the absence of bleeding, oral vitamin K may be administered.
Heparin-induced thrombocytopenia (HIT) and osteopenia are far less common with LMWH than with UFH. Thrombosis due to HIT should be managed with a direct thrombin inhibitor: Argatroban for patients with renal insufficiency and Lepirudin for patients with hepatic failure. In the setting of percutaneous coronary intervention, one should administer bivalirudin.
During pregnancy, warfarin should be avoided if possible because of warfarin embryopathy, which is most common with exposure during the sixth through twelfth week of gestation. However, women can take warfarin postpartum and breast-feed safely. Warfarin can also be administered safely during the second trimester.
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Complications of anticoagulation
Complication Management
Heparin Bleeding Stop heparin infusion. For severe bleeding, the anticoagulant effect of heparin can be reversed with intravenous protamine sulfate 1 mg/100 units of heparin bolus or 0.5 mg for the number of units given by constant infusion over the past hour; provide supportive care including transfusion and clot evacuation from closed body cavities as needed.
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Complications of anticoagulationComplication Management
LMWHs may have lower propensity to cause osteoporosis as compared with unfractionated heparin; consider LMWH if prolonged heparin therapy is necessary.
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Complications of anticoagulationComplication Management
Heparin Heparin-induced thrombocytopenia and thrombosis
Carefully monitor platelet count during therapy. Stop-heparin for platelet counts <75,000. Replace heparin with direct inhibitors of thrombin-like desirudin if necessary. These agents do not cause heparin-induced thrombocytopenia. Avoid platelet transfusion because of the risk for thrombosis.
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Complications of anticoagulation
Complication Management
Warfarin Bleeding Stop therapy. Administer vitamin K and fresh-frozen plasma for severe bleeding; provide supportive care including transfusion and clot evacuation from closed body cavities as needed
Skin necrosis (rare) Supportive care.
Teratogenicity Do not use in pregnancy or in patients planning to become pregnant.
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Important drug interactions with warfarin
Drugs that decrease warfarin requirement
Drugs that increase warfarin requirement
Phenylbutazone Barbiturates
Metronidazole Carbamazepine
Trimethoprim-sulfamethoxazole Rifampin
Amiodarone Penicillin
Second- and third-generation cephalosporins
Griseofulvin
Clofibrate Cholestyramine
Erythromycin
Anabolic steroids
Thyroxine
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Various inferior vena caval filters
Inferior Vena Caval Filters The two principal indications for insertion of an IVC
filter are (1) Active bleeding that precludes anticoagulation (2) Recurrent venous thrombosis despite intensive
anticoagulation It is not useful in PE as the filter itself may fail by
permitting the passage of small- to medium-size clots. Large thrombi may embolize to the pulmonary arteries via collateral veins that develop.
Paradoxically, by providing a nidus for clot formation, filters double the DVT rate over the ensuing 2 years after placement.
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Fibrinolysis Successful fibrinolytic therapy rapidly reverses right heart failure and
may result in a lower rate of death and recurrent PE by (1) dissolving much of the anatomically obstructing pulmonary arterial
thrombus (2) preventing the continued release of serotonin and other
neurohumoral factors that exacerbate pulmonary hypertension (3) lysing much of the source of the thrombus in the pelvic or deep leg
veins, thereby decreasing the likelihood of recurrent PE. The preferred fibrinolytic regimen is 100 mg of recombinant tissue
plasminogen activator (tPA) administered as a continuous peripheral intravenous infusion over 2 hours. Patients appear to respond to fibrinolysis for up to 14 days after the PE has occurred.
Contraindications to fibrinolysis include intracranial disease, recent surgery, and trauma. The overall major bleeding rate is about 10%, including a 1–3% risk of intracranial hemorrhage.
The only FDA-approved indication for PE fibrinolysis is massive PE
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Surgical Options Pulmonary Embolectomy : The risk of intracranial hemorrhage with fibrinolysis has prompted a
renaissance of surgical embolectomy. More prompt referral before the onset of irreversible cardiogenic shock and multisystem organ failure and improved surgical technique have resulted in a high survival rate. A possible alternative to open surgical embolectomy is catheter embolectomy. P
Pulmonary Thromboendarterectomy : Chronic thromboembolic pulmonary hypertension occurs in 2–4% of acute PE
patients. Therefore, PE patients who have initial pulmonary hypertension (usually diagnosed with Doppler echocardiography) should be followed up at about 6 weeks with a repeat echocardiogram to determine whether pulmonary arterial pressure has normalized. Patients impaired by dyspnea due to chronic thromboembolic pulmonary hypertension should be considered for pulmonary thromboendarterectomy, which, if successful, can markedly reduce, and at times even cure, pulmonary hypertension. The operation requires median sternotomy, cardiopulmonary bypass, deep hypothermia, and periods of hypothermic circulatory arrest. The mortality rate at experienced centers is approximately 5%.
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Post Phelibitic Syndrome It occurs in 15% of patients with deep vein thrombosis
(DVT). It presents with leg oedema, pain, nocturnal cramping, venous claudication, skin pigmentation, dermatitis and ulceration on the medial aspect of lower leg.
Daily use of below-knee 30- to 40-mmHg vascular compression stockings will halve the rate of developing postphlebitic syndrome. These stockings should be prescribed as soon as DVT is diagnosed and should be fitted carefully to maximize their benefit. When patients are in bed, the stockings need not be worn.
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HITTS• Clinicopathologic Syndrome:
• Unexplained 50% decrease in platelets (even if absolute total > 150)
• Positive test for Heparin antibodies• Activation assay (more relevant but more difficult)• Antigen assay
• Types:• Type I
• begins early (few hours) after starting heparin• typically benign with plts usually staying > 100K. No Rx needed.
• Type II• begins several days into treatment (unless previously sensitized)• High risk for thrombotic complications. Requires Rx.
