5/2/18 Updates in Hematology: Thrombosis & A Little Anemia 46 th Annual UCSF Advances in Internal Medicine Andrew D. Leavitt, MD May 10, 2018 Topic Outline 1. VTE – Comparing notes: What would you do? 2. Review of some AACP/Chest Guidelines 3. Direct Oral Anti-Coagulants (DOACs): A Little Review 4. DOACs and Patients with Cancer 6. Superficial Venous Thrombosis (SVT) 7. Anemia Cases – A Couple Cases from General Medicine 1
5/2/18 CASE 1: What Would You Do? Ø A 32 year old man comes to your office with 5 days of progressive discomfort in his left leg, and 2 days of swelling from the knee down. Ø No significant PMH. He takes no Rx. He cannot recall any particular injury other than having been kicked in the left leg while playing soccer 10 days previously. He is afebrile. Ø History and exam lead you to suspect a DVT. You ssend him for a left leg ultrasound Case 1 . Doppler ultrasound demonstrates occlusive thrombosis in the left femoral vein from the mid thigh distally into the popliteal vein. YOU WOULD?... 1. Start him on LMWH with bridge to warfarin. 2. Start LMWH & 1 week later switch to oral Dabigatran (PRDAXA) 3. Start him on oral Rivaroxaban (XARELTO) 4. Start him on oral Apixaban (ELIQUIS) 5. Start LMWH & 1 week later switch to oral Edoxaban (SAVAYSA) 6. Admit him to the hospital for treatment 7. Other 2
5/2/18 Case 2 . Same story as Case 1, but this time the ultrasound demonstrates occlusive thrombosis in the left posterior tibial and peroneal veins (deep veins of the calf) with no clot in the popliteal or femoral veins. YOU WOULD?...: 1. Start him on LMWH with bridge to warfarin. 2. Start LMWH & 1 week later switch to oral Dabigatran (PRDAXA) 3. Start him on oral Rivaroxaban (XARELTO) 4. Start him on oral Apixaban (ELIQUIS) 5. Start LMWH & 1 week later switch to oral Edoxaban (SAVAYSA) 6. Admit him to the hospital for treatment 7. Other Case 3 . Same guy, but this time, in addition, to the the ultrasound demonstrating occlusive thrombosis in the left femoral vein from the mid thigh distally into the popliteal vein, he admits to pleuritic chest pain over the past two days but denies SOB. A Chest CT Angiogram shows a L upper lobe segmental PE. BP 132/86, HR 89, RR 16, O2 Sat 98% on room air, EKG normal. 1. Start him on LMWH with bridge to warfarin. 2. Start LMWH & 1 week later switch to oral Dabigatran (PRDAXA) 3. Start him on oral Rivaroxaban (XARELTO) 4. Start him on oral Apixaban (ELIQUIS) 5. Start LMWH & 1 week later switch to oral Edoxaban (SAVAYSA) 6. Admit him to the hospital for treatment 7. Other 3
5/2/18 AACP/Chest Guidelines 10 th ed. 2016 1 Which Agent? In patients with proximal or isolated distal DVT of the leg, or PE, and no cancer, we suggest dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonist (VKA) anticoagulant therapy. If not treated with a DOAC, we suggest VKA over low molecular weight heparin (LMWH). 1. Kearon et al., Chest (2016) 149:315-52 DOACs and Bleeding – A Meta-analysis Compared to warfarin, DOACS were associated with a reduced rate of : -Major bleeding by ~28% -Intracranial and fatal hemorrhage by ~50% Chai-Adisksopha et al. Blood (2014) 124:2450-8 4
5/2/18 CASE 3: What Would You Do? We all agree he needs treatment, but for how long? 1. 3 months 2. 6 months 3. 12 months 4. 24 months 5. Indefinitely 6. Other AACP/Chest Guidelines 10 th ed. 2016 1 How Long? - Provoked In patients with a proximal DVT of the leg, or PE provoked by surgery, or nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period, (ii) treatment of a longer time-limited period (eg, 6, 12, or 24 months), or (iii) extended therapy (no scheduled stop date). In patients with a isolated distal DVT of the leg provoked by surgery or nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over shorter or longer treatment periods. BUT, it is anticipated that not all patients diagnosed with isolated distal DVT will be prescribed anticoagulants 1. Kearon et al., Chest (2016) 149:315-52 5
5/2/18 AACP/Chest Guidelines 10 th ed. 2016 1 How Long? – Unprovoked In patients with an unprovoked DVT of the leg (isolated distal or proximal) or PE , we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration, and we recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6, 12, or 24 months) In patients with a unprovoked proximal DVT or PE and who have a (i) low or moderate bleeding risk, we recommend extended anticoagulant therapy (no scheduled stop date) over 3 months. If a high bleeding risk, we suggest 3 months over extended therapy (no scheduled stop date). In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, we suggest aspirin over no aspirin to prevent recurrent VTE 1. Kearon et al., Chest (2016) 149:315-52 Bleeding Risk Assessment Kearon et al., Chest (2016) 149:315-52 (AACP/Chest Guidelines 10 th ed.) 6
5/2/18 Guidelines…are Guidelines…not Laws: They are where you start your thinking, not where you end it. METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence. CONCLUSIONS : Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research. Kearon et al., Chest (2016) 149:315-52 (AACP/Chest Guidelines 10 th ed.) Anticoagulation Care Tips 1. Everyone wants to know ‘how long?’ But you cannot please everyone. 2. I do not say life-long. Extended….indefinite…let’s see…? 3. What are the patient’s wants AND fears? 4. Extended use REQUIRES ongoing risk/benefit assessment. 5. DOACs and renal function! 6. DOACs and anti-platelet agents 7. Much we do not know. Admit and gain the patient’s confidence 7
5/2/18 A LITTLE DRUG REVIEW Coagulation Cascade in Patients Tissue Factor Tissue Factor Tissue Factor TF TF TF TF XI XIa VII IXa VIIa IX TF VIIIa Ca ++ /Pl TF/VIIa RivaroXaban ApiXaban Xa X EdoXaban Va = Warfarin BetriXaban Ca ++ /Pl IIa (Thrombin) II DabigaTran Fibrinogen Fibrin XIIIa X-linked Fibrin Tissue Factor Tissue Factor Tissue Factor 8
5/2/18 DOACs & Laboratory Testing We Lack Data Correlating Drug Level and Efficacy/Hemorrhage aPTT and PT : too insensitive, too sensitive, no clear dose response Direct Thrombin Inhibitor – Dabigatran: aPTT more sensitive than PT -But, not standardized and prolongation not predictable -And, normal aPTT does not rule out ‘on therapy’ drug level Thrombin Time is exquisitely sensitive If normal, then essentially no clinically significant drug in system Xa Inhibitors – Rivaroxaban, Apixaban & Edoxaban: PT is more sensitive than is the aPTT -But a normal PT does not rule out ‘on therapy’ drug level Need chromogenic Factor Xa activity assay standardized to the Rx No effect on Thrombin Time DOACs – A Few Summary Points to Start Ø All have a black box warning with two key points: § Premature discontinuation increases risk of thrombotic events These findings are from the Atrial Fibrillation trials Therefore: Parenteral bridging if DOAC to Warfarin § Spinal/Epidural Hematoma Need protocols for stopping/starting around procedures Ø Decline in renal function leads to increased bleeding risk § Think E lderly, N SAIDs, D ehydration/nausea/vomiting ( END ) Ø Be sure proceduralist is aware your patient is taking the medication Ø Not for use with mechanical heart valves Ø Patients need follow up but you lack the INR clinic connection 9
5/2/18 VTE in Cancer Patients Recurrent VTE & Bleeding on Anticoagulation Prandoni, et al. Blood 2002;100:3484-8 10
5/2/18 The CLOT Trial* -Recurrent VTE: 17% (OA) vs 9% (D) at 6 months HR 0.48 (0.3 – 0.77); P = 0.002 -Major Bleeding: 4% (OA) vs 6% (D); P = 0.27 -Any bleeding: 14% (OA) vs 19% (D); P = 0.09 -Mortality: 41% (OA) vs 39% (D) What about beyond 6 months? What about the belly ache of injections? *Lee et al. NEJM 2003;349(2)146-53 Raskob GE, et al. for the HOKUSAI VTE Cancer Investigators N Engl J Med 2018; 378:615-24 Katsushika Hokusai 11
5/2/18 Hokusai VTE Trial – Conclusion 1. Oral edoxaban is noninferior to subcutaneous dalteparin in terms of composite outcome of recurrent VTE or major bleeding 2. The rate of recurrent VTE was numerically lower with edoxaban: 7.9% vs 11.3%; HR 0.71 (0.48-1.06); P=0.09 3. The rate of major bleeding was significantly higher with edoxaban: 6.9% vs 4.0%; HR 1.77 (1.03-3.04); P=0.04 -Mostly due to UGI bleeding in patients with GI tumors -Dalteparin bleeds were lower in this trial than in other trials Hokusai VTE Trial – Cancer Types 12
5/2/18 Hokusai VTE Trial – Patient Characteristics Hokusai VTE Trial – Results VTE Combined Major Bleed or VTE MAJOR BLEED 13
5/2/18 Hokusai VTE Trial – Results - not a clinical emergency - not 1, 3, or 4 - yes clinical emergency – hemodynamic or CNS - death before or shortly after hospital admission Superficial Venous Thrombosis 14
Recommend
More recommend
