Updates in Hematology: Thrombosis & A Little Anemia 46 th Annual - - PDF document
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
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46th Annual UCSF Advances in Internal Medicine
Andrew D. Leavitt, MD
May 10, 2018
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
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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
5/2/18 3 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
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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).
Chai-Adisksopha et al. Blood (2014) 124:2450-8
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1. 3 months 2. 6 months 3. 12 months 4. 24 months 5. Indefinitely 6. Other
We all agree he needs treatment, but for how long?
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
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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
(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
Kearon et al., Chest (2016) 149:315-52 (AACP/Chest Guidelines 10th ed.)
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They are where you start your thinking, not where you end it.
Kearon et al., Chest (2016) 149:315-52 (AACP/Chest Guidelines 10th ed.)
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. 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.
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
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TF TF
XI XIa
Fibrinogen Fibrin X-linked Fibrin XIIIa
X II IIa (Thrombin) Xa Va
Ca++/Pl
TF/VIIa VIIa TF VII IX IXa VIIIa
Ca++/Pl
Tissue Factor Tissue Factor Tissue Factor Tissue Factor Tissue Factor Tissue Factor
TF TF = Warfarin
DabigaTran RivaroXaban ApiXaban EdoXaban BetriXaban
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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
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
Need chromogenic Factor Xa activity assay standardized to the Rx No effect on Thrombin Time
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 Elderly, NSAIDs, Dehydration/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
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Prandoni, et al. Blood 2002;100:3484-8
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17% (OA) vs 9% (D) at 6 months HR 0.48 (0.3 – 0.77); P = 0.002
6% (D); P = 0.27
41% (OA) vs 39% (D)
*Lee et al. NEJM 2003;349(2)146-53
What about beyond 6 months? What about the belly ache of injections?
Katsushika Hokusai
Raskob GE, et al. for the HOKUSAI VTE Cancer Investigators N Engl J Med 2018; 378:615-24
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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
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Combined Major Bleed or VTE VTE MAJOR BLEED
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MyHealth.Alberta.Ca
*The confusing “superficial femoral vein” segment of the deep vein system.
Ø A 32 year old man comes to your office with a 5 days of a cord-like ‘thing’ on his inner left thigh. Ø He has no significant past medical history and takes no
having been accidentally kicked in the left leg while playing soccer 2 weeks previously. He is afebrile. Ø You palpate the cord. It is tender and there is mild erythema. You suspect a blood clot and send him for a Doppler US.
5/2/18 16 Case 4. A Doppler Ultrasound demonstrates a 6 cm thrombus in the left saphenous vein. No DVT identified. You recommend:
1. Warm soaks, elevation, NSAID, & Follow up US 2. LMWH with bridge to warfarin x 6 weeks. 3. LMWH with bridge to warfarin x 12 weeks. 4. Fondaparinux or LMWH x 6 weeks. 5. Fondaparinux or LMWH x 12 weeks. 6. Rivaroxaban or Apixaban x 6 weeks 7. Rivaroxaban or Apixaban x 12 weeks 8. Other
Decousus, et al., NEJM 363(13):1222-32, 2010.
Cumulative Risk (%) Years since SVT Diagnosis PE DVT HR @ 3mo: 87 (70-108) HR @ 5 Yr: 6.3 (5.6-7) HR @ 3 mo: 45 (34-61) HR @ 5 Yr: 2.9 (2.5-3.5)
Cannegieter, et al., BLOOD 125:1229-35, 2015.
Treatment: 2.5mg qD fonda x45D vs placebo Events: 13/1502 (0.9%) vs 88/1500 (5.9%) (Sx PE, DVT, Extension to Jxn, Recurrence) Rel Risk Reduction: 85% (95% CI: 74-92) DVT & PE (0.2% vs 1.3%): Rel Risk Reduction: 85% (50-95) Rel Risk Reduction maintained at day 77. CALISTO Study Danish National Registry Study 10,973 patients with SVT vs. 515,067 in comparison cohort Again found DVT and PE risk. Increased risk of MI and CVA Suggests ‘systemic disorder’
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diagnosis of isolated SVT ≥5 cm in length in the lower extremity. – Grade 2B recommendation
– Grade 3B recommendation
*Chest 2012;141(2)(suppl):e419S-e494S
(i) extensive (ii) above knee (iii) greater saphenous vein (iv) near saphenofemoral jxn (v) severe symptoms (vi) History of VTE or SVT (vii) active cancer (viii) recent surgery
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62 yo man admitted for bilateral Total Hip Arthroplasty has the following pre-op CBC that shows an unexpected anemia. CBC: WBC: 7.1 Hgb 7.8 Hct 29.2 Plt 288 Consult to Heme: 1. Why is he anemic? 2. Please evaluate ASAP, patient in pain and needs surgery. 3. Surgery cancelled until you give us an answer. 4. He is a physician
How do you proceed? What do you want to know?
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64 yo woman: “Persistent microcytic anemia. Does she need a bone marrow biopsy?” Most recent CBC that prompted the referral:
3 - 10 x 109/L 4 - 5.2 x 1012/L 4.4 – 5.9 x 1012/L 12 - 15.5 g/dL 13.6 – 17.5 g/dL 36 - 46%; 41 - 53% 80-100 fL
NORMAL VALUES
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*Gives insight into marrow and possible need for BM BX
Andrew D. Leavitt, MD 415-514-3432 andrew.leavitt@ucsf.edu