1. A 35-year-old man presented with acute onset of breathlessness and was found to have pulmonary thromboembolism and deficiencies in protein C and protein S without evidence of deep vein thrombosis. 2. He was treated with supportive measures, heparin, acenocoumarol, and supplements but developed massive hemoptysis and succumbed to his illness despite intensive care. 3. The case report discusses evaluation, treatment, and long-term management of venous thromboembolism and highlights complications that can arise.

1. TWO CASES WITH HEMOPTYSIS CASE 2 PROF.S.SUNDAR’S UNIT Dr.V.Jayaprakash

2. Mr.Marimuthu, 35 years,lorry driver,admitted on 12.2.2009 C/O Breathlessness – 1 day H/O Presenting illness: The patient was apparently alright 1 day back when he developed acute onset of breathlessness,stationary in course,class 4,aggravated by exertion and relieved by rest and sitting posture H/O orthopnea No H/O chest pain No H/O palpitation/syncope/pedal edema

3. No H/O cough/hemoptysis/wheeze No H/O fever No H/O abdominal pain/abdominal distension/oliguria No H/O swelling of legs PAST H/O : No H/O of similar illness in the past No H/O recent surgery/travel/immobility No H/O DM/SHT/bronchial asthma/TB/CAHD/CVA/ seizure disorder H/O vascular disease of right lower limb 5 years back for which he had undergone bypass surgery

4. PERSONAL HISTORY: Mixed diet Smoker for 10 years; smokes one pack per day Occasionally consumes alcohol FAMILY HISTORY: Nil significant TREATMENT HISTORY: Nil significant

5. GENERAL EXAMINATION Conscious Oriented Afebrile No pallor Central cyanosis No clubbing Dyspneic and tachypneic No pedal edema/calf muscle tenderness No generalised lymphadenopathy BP – 110/80 mmHg PR – 120/min Dorsalis pedis and posterior tibial pulsation absent in both lower limbs RR – 35/min JVP – Not elevated

6. CARDIOVASCULAR SYSTEM: S1S2 heard No murmurs RESPIRATORY SYSTEM: NVBS heard No added sounds ABDOMINAL EXAMINATION: Soft Midline scar+ No organomegaly/ Free fluid CENTRAL NERVOUS SYSTEM: No focal neurological deficit

7. PROVISONAL DIAGNOSIS ACUTE BREATHLESSNESS FOR EVALUATION ? Pulmonary Thromboembolism No evidence of DVT clinically

9. INVESTIGATIONS Urine routine – Normal CBC: Hb – 13 g% TC – 12000 DC – P85 L16 E4 ESR – 5/12 PCV – 42% Platelet – 1.2 lakh Blood sugar ®- 107mg% Urea – 27 mg% Sr creatinine – 0.8 mg% Sr Na+ - 140 mmol/l K+ - 4.1 mmol/l Sr Lipid profile – 186 mg%

10. ECG on admission

11. Chest X ray PA view

12. CHEST X RAY PA VIEW Prominent pulmonary artery ECG Sinus tachycardia RBBB S1 Q3 T3 pattern ST segment depression in lead I and ll ST segment depression in left precordial leads Tall R waves in right precordial leads

13. ECG FINDINGS IN PULMONARY EMBOLISM Low amplitude deflection Right atrial enlargement Right ventricular hypertrophy Right ventricular myocardial ischemia Right ventricular myocardial injury RBBB Atrial tachyarrythmias

14. ECG FINDINGS IN PULMONARY EMBOLISM FRONTAL PLANE LEADS: S1Q3T3 pattern ST segment depresson in standard lead l and ll Right axis deviation Tall peaked T wave in lead ll HORIZONTAL LEADS: T wave inversion in right precordial leads ST segment elevation in right precordial leads ST segment depression in left precordial leads Increase in R amplitude in right precordial leads RBBB

15. ECHOCARDIOGRAM: No RWMA Normal LV systolic function TR mild TRPG 48 mmHg Mild RA/RV dilated D-DIMER LEVEL: 3.27 microgram/ml – POSITIVE (Normal : < 0.5 mcg/ml)

16. FURTHER INVESTIGATIONS CT Chest – Normal study Doppler study of both lower limbs – No evidence of DVT Lupus anticoagulant – Negative Anti CardioLipin Antibody (ACLA) – Normal IgG – 5.11 GPLU/ml (Normal - < 10) IgG – 3.65 mPLU/ml (Normal - <7) Protein C levels – 44.6% (Normal :70 – 140%) Protein S levels – 39.7% (Normal : 60 – 150%) Sr homocysteine level – 20.31 mcmol/l (Normal:5.9 – 16) Antithrombin levels – Not done Factor V Leiden – Not done 15/2/09 18/2/09 23/2/09 PT 17.6 26.3 24.2 aPTT 36.4 40 40.5 INR 1.6 2.8 2.68

18. FINAL DIAGNOSIS PULMONARY THROMOEMBOLISM PROTEIN C DEFICIENCY PROTEIN S DEFICIENCY NO DEEP VENOUS THROMBOSIS

19. TREATMENT GIVEN Supportive measures Unfractionated Heparin Acenocoumarol Folic acid tablets B – complex supplements

20. VENOUS THROMBOEMBOLIC DISORDERS (DVT & PE) ETIOLOGY: Stasis, Hypercoagulability, Venous endothelial injury STASIS : Immobilisation (Trauma,Surgery,Immobilisation) HYPERCOAGULABLE STATES : Inherited : Prothrombin gene mutation, partial protein C deficiency, partial protein S deficiency, partial antithrombin deficiency,factor V Leiden, hyperhomocystinemia Acquired : Malignancy, nephrotic syndrome, estrogen use, pregnancy, HIT,APA syndrome, sickle cell disease, marrow fat embolism, amniotic fluid embolism

21. CLINICAL PRESENTATION (Signs and symptoms of DVT & PE are neither sensitive nor specific) CLINICAL DECISION RULES: Clinical variable Score Signs and symptoms of DVT 3.0 Alternative diagnosis less likely than PE 3.0 Heart rate >100/min 1.5 Immobilisation>3 days,Surgery within 4 wks 1.5 Prior PE or DVT 1.5 Hemoptysis 1.0 Cancer 1.0 High clinical likelihood of PE if the point score exceeds 4.0

22. ASSESSMENT OF SEVERITY OF PE MASSIVE PE: Systemic Arterial Hypotension MODERATE TO LARGE PE: RV Hypokinesias in Echocardiography Normal Systemic Arterial Pressure SMALL TO MODERATE PE: Normal Right Heart Function Normal Systemic Arterial Pressure

23. LABORATORY STUDIES D-DIMER: Cross linked fibrin degradation product that may be increased during acute illness or VTE. It has a low positive predictive value and specificity – If positive, requires further evaluation. It has high negative predictive value-If negative,it excludes DVT.

24. LABORATORY ASSESSMENT OF INHERITED THROMBOPHILIC STATES Prothrombin gene mutation G20210A G20210A mutation Partial protein C deficiency Partial protein S deficiency Protein C activity Protein S activity, Free protein S antigen Factor V Leiden Activated protein C resistance, if positive confirm with Factor V Leiden PCR Hyperhomocystinemia Fasting plasma homocysteine levels

25. LABORATORY ASSESSMENT OF ACQUIRED THROMBOPHILIC STATES ANTIPHOSPHOLIPID ANTIBODY SYNDROME LUPUS ANTICOAGULANT, ANTICARDIOLIPIN ANTIBODY, BETA 2 GLYCOPROTEIN 1 PNH RBC OR WBC FLOW CYTOMETRY FOR LOSS OF CD55,CD59 MYELOPROLIFERATIVE DISORDER JAK – 2 MUTATION

26. IMAGING - DVT SPECIFIC TESTING Duplex Examination - Compressive ultrasound performed with doppler testing Venography MRI CT Venography

27. PE SPECIFIC TESTING NONSPECIFIC TESTS: ~ ECG,Troponin levels, Chest Radiography ~ Determine pretest probability of PE along with D-Dimer assay CONTRAST ENHANCED SPIRAL(HELICAL) CHEST CT: ~ Relatively accurate for large(proximal) PE, but sensitivity is low for small(distal) emboli ~ Clinical suspicion that is discordant with the objective finding should lead to further testing

28. V/Q SCANNING: Requires administration of radioactive material(via both inhaled and i.v. routes) V/Q scan can be classified as normal, non diagnostic or high probability for PE Use of clinical suspicion improves the accuracy of V/Q scan When both the findings are discordant, further testing should be performed MR ANGIOGRAPHY PULMONARY ANGIOGRAPHY

29. TREATMENT UNFRACTIONATED HEPARIN (UFH): 80 U/kg bolus followed by infusion of 18 U/kg/hr. Continued for atleast 4-5 days and until INRs of atleast 2 are achieved on 2 consecutive days with warfarin therapy. LMWH: VKAs(Vitamin K Antagonists), Warfarin or Acenocoumarol: Started as 5 mg PO and dose adjusted according to INR INR should be done frequently during the first month,because multiple dose adjustments are usually necessary to achieve therapeutic INR Once a stable dose is achieved, INR monitoring should be done atleast 4 weeks.

30. THROMBOLYTIC THERAPY- INDICATIONS: Refractory Systemic Hypotension ? Right Ventricular Dysfunction ANTITHROMBIN III INFUSION: In patients with congenital antithrombin lll deficiency - during an acute thromotic episode

31. INVASIVE SPECIAL THERAPIES IVC FILTERS: 1] Acute DVT states in which there is absolute contraindication to anticoagulation 2] Recurrent thromboembolic episodes CATHETER EMBOLECTOMY SURGICAL EMBOLECTOMY

32. LONG TERM TREATMENT WITH VITAMIN K ANTAGONISTS FOR DVT AND PE First episode of DVT or PE secondary to a transient risk factors 3 mon Recommendation applies to both proximal and calf vein thrombosis First episode of idiopathic DVT or PE 6 – 12 mon Continuation of therapy after 6 -12 mon to be considered First episode of DVT or PE with a documented thrombophilic abnormality 6 – 12 mon Continuation of therapy after 6 -12 mon to be considered First episode of DVT or PE with documented antiphospholipid or >= 2 thrombophilic abnormality 12 mon Continuation of therapy after 12 mon to be considered

33. COURSE OF THE ILLNESS His breathlessness improved, was able to walk about 100 m without breathlessness. Except for sinus tachycardia, ECG features of PE disappeared. He was discharged at request on 27.2.2009 with advice to continue acitrom and to get readmitted after 3 days for planning CT Angiogram. But he came for admission the next day itself with massive hemoptysis; cause - ?acitrom related ?massive pulmonary embolism and infarct. He was treated with vitamin K, FFP and blood transfusion; shifted to IMCU for intensive care. Evaluation revealed prolonged coagulation parameters. PT- 48 seconds, INR- 4.3. Massive hemoptysis recurred and the patient had hypoxia and altered sensorium. Despite the best possible efforts, the patient succumbed to his illness.

35. ACKNOWLEDGEMENTS THE PATIENT AND HIS FAMILY IMCU TEAM

36. thank you