Venous thromboembolism

VENOUS THROMBO EMBOLISMDr shams Rehan

WHAT IS VENOUS THROMBOSIS

THROMBOSIS IS A BLOOD CLOT IN A BLOOD VESSEL, A VEIN OR AN ARTERY DEEP VEIN THROMBOSIS (DVT) IS A BLOOD CLOT THAT FORMS IN A DEEP VEIN OF THE LEG, CALF OR PELVIS.VIRCHOWS TRIADHYPERCOAGULABILITYVENOUS STASISVASCULAR DAMAGEINCREASED VON WILLIEBRAND FACTORINCREASES IN FACTORS VII, IX, X, XIIINCREASED FIBRINOGENREDUCED PROTEIN SACQUIRED PROTEIN C RESISTANCEIMPAIRED FIBRINOLYTIC ACTIVITYTHE PATHOGENESIS OF PREGNANCY-ASSOCIATED VTE.

RISK FACTORS FOR VENOUS THROMBOEMBOLISM INPREGNANCYPRE-EXISTINGOBSTETRICNEW-ONSET/TRANSIENT POTENTIALLY REVERSIBLERISK FACTORS FOR VENOUS THROMBOEMBOLISM INPREGNANCY PRE-EXISTING THROMBOPHILIAIS THE TERM APPLIED TO THE CONDITION IN WHICH PATIENT HAD THE DEFECTS OR ABNORMALITIES THAT ALTER THE PHYSIOLOGICAL HAEMOSTATIC BALANCE IN FAVOUR OF FIBRIN FORMATION OR PERSISTENCE &HENCE INCREASES THE RISK OF THROMBOSIS CONGENITALAntithromboin deficiencyProtein C deficiencyActivated Protein C deficiencyProtein S deficiencyFactor V LeidenProthrombin gene variant

ACQUIREDLupus anticoagulantAnticardiolipin antibodiesRISK FACTORS FOR VENOUS THROMBOEMBOLISM INPREGNANCY PRE-EXISTINGMEDICAL COMORBIDITIES (e.g. heart or lung disease, SLE, cancer, inflammatory conditions (inflammatory bowel disease or inflammatory polyarthropathy), nephrotic syndrome (proteinuria > 3 g/day), sickle cell disease,36 intravenous drug userAGE > 35 YEARSOBESITY (BMI > 30 kg/m2) either prepregnancy or in early pregnancyPARITY 3SMOKINGGROSS VARICOSE VEINS (symptomatic or above knee or with associated phlebitis, oedema/skin changes)PARAPLEGIA

RISK FACTORS FOR VENOUS THROMBOEMBOLISM INPREGNANCY OBSTETRIC MULTIPLE PREGNANCY,ASSISTED REPRODUCTIVE THERAPYPRE-ECLAMPSIACAESAREAN SECTIONPROLONGED LABOUR, MID-CAVITY ROTATIONAL OPERATIVE DELIVERYPPH (> 1 LITRE) REQUIRING TRANSFUSIONNEW-ONSET/TRANSIENT SURGICAL PROCEDURE IN PREGNANCY OR PUERPERIUM (E.G. ERPC, APPENDICECTOMY, POSTPARTUM STERILISATION)POTENTIALLY REVERSIBLEA HYPEREMESIS, DEHYDRATIONOVARIAN HYPERSTIMULATION SYNDROME (OHSS)ADMISSION OR IMMOBILITY ( 3 DAYS BED REST) E.G. SYMPHYSIS PUBIS DYSFUNCTION RESTRICTING MOBILITYSYSTEMIC INFECTION (REQUIRING ANTIBIOTICS OR ADMISSION TO HOSPITAL) E.G. PNEUMONIA, PYELONEPHRITIS,POSTPARTUM WOUND INFECTIONLONG-DISTANCE TRAVEL (> 4 HOURS)VENOUS THROMBO EMBOLISM (VTE)Gestational deep venous thrombosis (DVT) usually occurs in THE ILEO-FEMORAL VEINS (70 versus 9% in the non-pregnant) and is therefore more likely to result in pulmonary embolism (PE). Furthermore, it is also MORE LIKELY TO OCCUR IN THE LEFT LEG (85 versus 55% in the non pregnant), perhaps related to compression of the left iliac vein by the right iliac artery.

CLINICAL FEATURES & DIAGNOSISCALF THROMBOSIS

UNILATERAL LEG SWELLING AND PAINON EXAMINATIONCalf is TENDER& INDURATED on palpationHIGHER SKIN TEMPERATURE on affected side b/c most of the venous return take place through superficial veinsLEG CIRCUMFERENCE measurement at identical site difference of >2 cm is significantThe limb DISTAL PART IS PALE or cyanosedCLINICAL FEATURES & DIAGNOSIS ILIOFEMORAL THROMBOSISMORE COMMON THAN CALF THROMBOSISLeg swelling & pain but more symptomaticGrossly swollen & painful leg (white leg or phlegmasia alba dolens)The femoral vein course is tenderDilated superficial veinsDistal limb is pale , cynanosed with reduced or absent venous pulses secondary to arterial spasmDIAGNOSIS OF DVT IS DIFFICULT

OFTEN ASYMPTOMATIC, ONLY HALF OF THE PATIENTS HAVE DEMOSTRABLE SYMPTOMSON THE OTHER HAND 25-50% 0F PATIENTS WITH CLINICAL SIGNS OF THROMBOSIS HAVE NO DEMOSTRABLE VENOUS THROMBOSIS

INVESTIGATIONSDOPPLER ULTRASOUNDULTRASONOGRAPHYPLETHYSMOGRAPHYVENOGRAM

DOPPLER U/S

PULMONARY EMBOLISM

PULMONARY EMBOLISM CLINICAL FEATURES OF PULMONARY EMBOLISM ARE HIGHLY VARIABLE DEPENDING ON SIZE OF EMBOLUS& THE PRECEDING HEALTH OF THE PATIENTThe symptom & sign of pulmonary embolism are predominately associated with the CVS & RESPIRATORY SYSTEMS

WARNING SYMPTOMS&SIGNS OF SMALL PULMONARY EMBOLUS

UNEXPLAINED PYREXIATACHYCARDIASYNCOPECOUGHCHEST PAINBREATHLESSNESS

CLINICAL FEATURES OF MASSIVE PULMONARY EMBOLISMSEVERE CHEST PAINAIR HUNGER , extreme apprehension& sudden collapse due to decreased cerebral blood flowPREDOMINANT SIGNS Cyanosis , raised JVP, rapid breathingPleuritic chest fricition on auscultationExcessive purulent sputum & high temprature is most likely due to infective pleurisySyncope results from decreased cerebral blood flow b/c of obstruction in the pulmonary vasculatureECG

DEEP S WAVE IN LEAD I,Q WAVE & INVERTED T WAVE IN LEAD III, RIGHT AXIS DEVIATION, NOT DIAGNOSTIC

CHEST X-RAY : presence of consolidation , elevated hemi diaphragm on the affected side, not diagnostic

WHERE THERE IS CLINICAL SUSPICION OF ACUTE PTE A CHEST X-RAY SHOULD BE PERFORMED.ABNORMAL FEATURES CAUSED BY PTEATELECTASIS, EFFUSION, FOCAL OPACITIES, REGIONAL OLIGAEMIA OR PULMONARY OEDEMA.MAY IDENTIFY OTHER PULMONARY DISEASE PNEUMONIA, PNEUMOTHORAX OR LOBAR COLLAPSE2. COMPRESSION DUPLEX DOPPLER SHOULD BE PERFORMED WHERE THIS IS NORMAL. IF BOTH TESTS ARE NEGATIVE WITH PERSISTENT CLINICAL SUSPICION OF ACUTE PTEVENTILATIONPERFUSION (V/Q) LUNG SCAN OR COMPUTED TOMOGRAPHY PULMONARY ANGIOGRAM (CTPA) SHOULD BE PERFORMED.Women with suspected PTE should be advised that V/Q SCANNING CARRIES A SLIGHTLY INCREASED RISK OF CHILDHOOD CANCER compared with CTPA (1/280,000 versus less than 1/1,000,000) but carries a lower risk of maternal breast cancer (lifetime risk increased by up to 13.6% with CTPA, background risk of 1/200 for study population).Where feasible, women should be involved in the decision to undergo CTPA or V/Q scanning.IDEALLY,INFORMED CONSENT SHOULD BE OBTAINED BEFORE THESE TESTS ARE UNDERTAKEN.

21V/Q SCAN

VENTILATION- PERFUSION SCAN: In PE there is abnormal perfusion with normal ventilation scan. Krypton 81 m is isotope for ventilation & Tc 99 for perfusionTHE ISOTOPES HAVE VERY SHORT HALF LIFE , THEREFORE RADIATION RISK TO FETUS IS VERY LOWV/Q SCAN

Pulmonary embolisminvestigationsMRI : has advantage of direct imaging of thrombi in the pulmonary arteries & large veins with advantage of lack of ionizing radiationPULMONARY ANGIOGRAPHY : DEFINITE METHOD OF IDENTIFYING PULMONARY EMBOLISM if one of the two finding is present 1- intravascular filling defect or 2- pulmonary arterial vessle cut off but invasive procedure so inconvenient

In summary, DUPLEX DOPPLER U/S combined with VENOGRAPHY , are the most widely used test for the diagnosis of DVT & V/Q scan for the diagnosis of pulmonary embolism

ALL WOMEN SHOULD UNDERGO A DOCUMENTED ASSESSMENT OF RISK FACTORS FOR VTE IN EARLY PREGNANCY OR BEFOREPREGNANCY

ANTENATAL ASSESMENT & MANAGEMENT TO BE ASSESSED AT BOOKING & REPEATED IF ADMITTED

ANTENATAL ASSESMENT & MANAGEMENT HIGH RISK

SINGLE PREVIOUS VTE plusTHROMBOPHILIA OR FAMILY HISTORYUNPROVOKED/ESTROGEN RELATED PREVIOUS RECURRENT VTE( >1) REQUIRES ANTENATAL PROPHYLAXIS WITH LMWHMX BY THROMBOSIS EXPERT TEAM

CONSIDER ANTENATAL PROPHYLAXIS WITH LMWHMX BY THROMBOSIS EXPERT TEAM

ANTENATAL ASSESMENT & MANAGEMENTLOW RISKAge 30kg/m2)Parity >3SmokerGross varicose veinsCurrent systemic infectionImmobilityLong distance travelPre-eclampsiaDehydration/HEG/OHSSMULTIPLE PREGNANCY/ART

3 OR MORE RISK FACTORS2 OR MORE RISK FACTORS IF ADMITTED

INTERMEDIATE RISK

< 3 RISK FACTORS

LOWER RISK MOBILISATION & AVOIDANCE OF DEHYDRATIONPOSTNATAL ASSESMENT & MANAGEMENTTO BE ASSESSED ON DELIVERY SUITEOBSTETRIC THROMBOPROPHYLAXIS RISK ASSESMENT &MANAGEMENTPOSTNATAL ASSESMENT & MANAGEMENTHIGH RISK

ANY PREVIOUS VTEANYONE REQUIRING ANTENATAL LMWHREQUIRES AT LEAST 6 WEEKS POSTNATAL PROPHYLAXIS WITH LMWH

AT LEAST 7 DAYS POSTNATAL PROPHYLAXIS WITH LMWHIF PERSISTING OR > 3 RISK FACTORS,CONSIDER EXTENDING PROPHYLAXIS WITH LMWHPOSTNATAL ASSESMENT & MANAGEMENTTO BE ASSESSED ON DELIVERY SUITEOBSTETRIC THROMBOPROPHYLAXIS RISK ASSESMENT &MANAGEMENTAge 30kg/m2)Parity >3SmokerGross varicose veinsCurrent systemic infectionImmobilityLong distance travelPre-eclampsiaPROLONGED LABOUR2 OR MORE RISK FACTORS

INTERMEDIATE RISK

< 2 RISK FACTORS

LOWER RISK MOBILISATION & AVOIDANCE OF DEHYDRATIONANTICOAGULANTSantithrombics fibrinolytic and thrombolytics) are a class of drugs that work to prevent thecoagulation(clotting) of blood.It was originally isolated from caninelivercells, hence its name (heparor "" is Greek for "liver").Coagulation(thrombogenesis) is the process by whichbloodformsclots.Heparin is a naturally occurring anticoagulant produced bybasophilsandmast cells.[12]Heparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin does not break down clots that have already formed (unliketissue plasminogen activator), it allows the body's naturalclot lysismechanisms to work normally to break down clots that have formed.

MECHANISM OF ACTIONHEPARIN

Heparin and its low-molecular-weight derivatives (e.g.,enoxaparin,dalteparin,tinzaparin) are effective at preventing deep vein thromboses and pulmonary emboli in patients at risk.Heparin binds to the enzyme inhibitorantithrombinIII (AT), causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop.[16]The activated AT then inactivates thrombinand other proteases involved in blood clotting, most notablyfactor Xa. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin.[17]

ANTIDOTE TO HEPARIN OVERDOSEProtamine sulfate(1mg per 100 units of heparin that had been given over the past four hours) has been given to counteract the anticoagulant effect of heparin.COUMARINS (VITAMIN K ANTAGONISTS)

These oral anticoagulants are derived fromcoumarin, which is found in many plants. A prominent member of this class iswarfarin(Coumadin). It takes at least 48 to 72 hours for the anticoagulant effect to develop. Where an immediate effect is required,heparinmust be given concomitantly. These anticoagulants are used to treat patients withdeep-vein thrombosis(DVT),pulmonary embolism(PE) and to prevent emboli in patients withatrial fibrillation(AF),mechanicalprosthetic heart valves.

TREATMENT GENERAL MEASURES DVT

REST in left lateral position to avoid further stasis by gravid uterusElevated affected leg to facilitate venous returnFirm bandage of affected sideMobilization & leg exercises are of vital importance in opening up colateral venous channels& major factor in preventing long term venous insufficiencyONCE antithrombotic treatment is started, the clott become adherent to vessel wall and there is no risk for dislodgementprogressive ambulation after initiation of antithrombotic treatment once the leg symptoms allowSPECIFIC THERAPYA-ACUTE INITIAL PHASE TREATMENT1-ANTICOAGULANTS2- THROMBOLYTIC THERAPY3- SURGERY(THROMBECTOMY)

B-CHRONIC PHASE TREATMENTUNFRATIONATED HEPARINLMWHWARFARIN

SPECIFIC THERAPYTaking the general measures for DVT & after emergency resuscitation for pulmonary embolism, the treatment of both DVT & pulmonary embolus may be divided intoINITIAL ACUTE PHASE LASTING UPTO A WEEKCHRONIC PHASE TREATMENT LASTING FOR SEVERAL MONTHSSPECIFIC THERAPYACUTE INITIAL PHASE TREATMENT

HEPARIN: the drug of choice for thrombo-embolism during pregnancy b/cIt does not cross placentaNo influence on fetal coagulation systemIt does not have any role in re-absorption of thrombusIt is given to prevent further fatal episodesTwo forms of heparin availableUNFRACTIONATED HEPARININITIAL I/V BOLUS OF 5000 FOLLOWED BY 40,000 UNITS/DAY ( 1600U/H) BY CONTINOUS INFUSIONThe aim of treatment is to DOUBLE APTT, of its normal, which is achieved with serum heparin level of 0.2-0.6 IU/ml.Heparin should be given in NORMAL SALINE as it is not stable in dextrose infusion.Heparin INFUSION is better as intermittent injections produces in heparin levelSIDE-EFFECTS OF ACUTE THERAPY ARE bleeding & hypotension( due to cholorobutol- a preservative used in heparin)

UNFRACTIONATED HEPARINIF IT IS NECESSARY TO REVERSE THE EFFECT OF HEPARIN THERAPY

DISCONTINUATION OF HEPARIN therapy alone is sufficient as the half life of heparin is only 1.5 hrsHeparin is usually undetectable in blood 6 hours after discontinuation of therapyPROTAMINE SULPHATE is antidote in urgent situationNo more than 50 mg of protamine sulphate should be given in 10 mint period as protamine itself can cause bleedingFFP is an effective treatment modality for combination with or as an alternative to protamine sulphateLMWHADVANTAGESADMINISTERED IN SINGLE DAILY SUBCUTANEOUS DOSEPATIENT CAN HAVE AMBULATORY TREATMENTNO STRICT DOSE MONITORING BY REPEATED APTT TREATMENT ITS EFFICACY IS MONITORED BY ANTI Xa LEVELTHE INITIAL PHASE HIGH DOSE HEPARIN RX IS CONTINUED FOR 7-14 DAYS,DEPENDING ON SEVERITY OF INITIAL EPISODE & ANY EVIDENCE FOR RECURRENCEIT HAS LONGER HALF- LIFE& EFFECTS CONTINUES UPTO 24 HOURS AFTER DISCONTINUATION OF TREATMENTFOR ITS REVERSAL IN CASE OF BLEEDING, BOTH DISCONTINUATION & PROTAMINE SULPHATE IS NEEDED THROMBOLYTIC THERAPYSTREPTOKINASEUSE IS RESTRICTED ONLY IN LIFE THREATENING PULMONARY EMBOLISM

PULMONARY EMBOLUS for massive pulmonary embolus STANDARD CPR PROCEDURE IS NEEDEDintubationOxygenation with embo bagcardiac massageI/V lines & I/V heparin

SURGERYDVT: THROMBECTOMY IS ONLY JUSTIFIED WHEN LIMB SWELLING IS SO GREAT TO CAUSE GANGRENEINSERTION OF VENA CAVA FILTER PULMONARY EMBOLECTOMY: is indicated in the presence of following features one hour after initial eventSystolic BP of < 90 mmHgpaO2 < 60 mmHgUrine output < 20 ml/hr

THE SEQUENCE OF MANAGEMENT OF FATAL PULMONARY EMBOLISM1- TO CARRY OUT PULMONARY ANGIOGRAPHY AT WHICH CLOTT BREAKDOWN IS ATTEMPTED WITH GUIDE WIRE2- IN CASE OF ITS FAILURE ,THROMBOLYTIC THERAPY IS GIVEN3- SURGERY IS CARRIED ONLY AFTER THE FAILURE OF ABOVE TREATMENT