It's day 2 of the American Heart Association 2016 Scientific Sessions. I've been wandering around the convention center like a desperate romantic on a speed date trying to find a tantalizing trial or discussion. Alas, like my grandmother who was married five times (rest her soul), I fell in love with too many trials too easily and so am left trying to sort how to best relate all the great information I stumbled upon this morning.
It's not that there weren't tempting choices in today's press conference. Dr Michael Gibson (Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA) eloquently presented the data on the veritable Rubik's cube of strategies for anticoagulation in PCI patients. Low-dose rivaroxaban plus dual antiplatelet therapy (DAPT) beat warfarin plus DAPT. Hmmm . . . I liked that, but it's fairly technical and not a lot of room for opinion. I then considered FUTURE but couldn't really explain why eyeballing an angiogram and using a stress exam (or not) could beat fractional flow reserve (FFR) for directing revascularization strategy. Turns out, like many relationships, it might all have been due to chance, as Aronow the commenter suggested. I was intrigued at the ART results and how the deluxe RIMA/LIMA combination could not beat a single IMA approach. Perhaps the follow-up is too short. Perhaps it's due to better pharmacology for CAD since the 1980s when a LIMA beat the socks off saphenous vein grafts (SVGs) alone. I had to leave for another presentation before the GARY trial, so GARY and I never really had a chance. I folded my napkin, gulped the last drop of my second cup of coffee and left in hunt of a topic I could commit to (for today at least).
In room 224 I found a discussion on hypercoagulable states with primo experts like Dr Samuel Z Goldhaber (Harvard Medical School, Boston, MA), Dr John Bartholomew (Cleveland Clinic, OH) and Dr Ana Casanegra (Mayo Clinic, Rochester, MN). Dr Goldhaber started with a case presentation of a young female desperate to have a child who experienced a deep vein thrombosis (DVT) while undergoing in vitro fertilization (IVF) and a saddle pulmonary embolism (PE) treated initially with IV heparin followed by enoxaparin and then warfarin for 6 months. The patient was found to be heterozygous for factor V Leiden mutation.
The factor V Leiden mutation is kind of like my neighbor. I know he exists but I've rarely seen him. I check my window often to see if he's there, thinking it's really none of my business, and so it goes for factor V Leiden mutations assays. The mutation occurs at a rate of 5.3% in the US white population, 2.2% in Hispanics, 1.2% in African Americans, and 0.4% in Asians. Yet countless healthcare dollars are spent in quest of it. We should be suspicious in women with a pattern of recurrent first-trimester pregnancy loss without an obstetrical or genetic explanation, which reminded me that I need to be taking a pregnancy history more often in my female patients. I was impressed by the horror show of slides of placental thromboses, clotted umbilical cords, and fibrotic uteri shown to emphasize that factor V Leiden mutation doubles the risk for recurrent pregnancy loss.
Dr Goldhaber reviewed a landmark trial comparing enoxaparin 40 mg with aspirin 100 mg, showing a 29% live birth rate with aspirin vs a staggering 86% live birth rate with low-molecular-weight-heparin (LMWH) therapy. He described his approach for the unfortunate woman with the venous thromboembolism (VTE) during IVF. He treated her with 40 mg of LMWH preceding conception continuing for 6 weeks' postpartum. Dr Goldhaber announced that "a healthy baby boy was delivered," and obviously could not contain his jubilance at the retelling of that outcome.
Then we heard from Dr Bartholomew of the on heparin-induced thrombocytopenia (HIT). Although I've blamed falling platelet counts on heparin many times, I've never seen a "ghostly white clot"–laden catastrophe. Dr Bartholomew produced impressive slides of double amputees, failed inferior vena cava (IVC) filters, and dark necrotic limbs that should prompt more diligence about avoiding unnecessary or overly lengthy anticoagulation strategies. He described the 4T scoring system:
Thrombocytopenia with an absolute platelet count drop by 50%.
Timing—Days 5 to 10 of heparin therapy are the most common window of occurrence.
Thrombosis evidence—Arterial and venous.
Thrombocytopenia—Other possible causes.
He outlined the approach for suspected HIT that includes immediate cessation of unfractionated heparin (UFH), starting another anticoagulant, obtaining an anti-PF4 heparin ELISA test, followed by a functional assay if positive and if negative our need to consider an alternative diagnosis and resume heparin.
HIT is serious business, because there is a 6.1% incidence of death, amputation, or thromboembolism for every day the patient remains on heparin. And heparin cessation alone is not enough because the 30-day risk of subsequent thrombotic events can be as high as 52% in some studies.
Dr Bartholomew reminded us to discontinue the use of heparin-coated catheters, LMWH, and flushes and then choose appropriate therapy. He flew through slides discussing the need to stop warfarin; to use vitamin K in warfarin-treated patients; and that treatment options include fondaparinux, argatroban, and bivalirudin. He talked about a study in 22 patients on combination therapy with any of the full-dose NOAC regimens and 32 hours+4 hours of argatroban. Amazingly there was no bleeding, limb loss, or recurrent VTE in that small trial. He then reiterated that we should avoid warfarin until platelet counts have recovered to >150K. To restart warfarin, he recommended a low 5-mg dose with a minimum 5-day overlap with a direct thrombin inhibitor (DTI) and reminded us to not stop the DTI until the INR is therapeutic for two consecutive days.
An audience member asked, "If the platelet count is very low would you be keen to start them on anticoagulation?" Dr Bartholomew replied, "Depends on how low. Most are usually 30K or more, yet on occasion we do see profound thrombocytopenia and they usually don't bleed. We've thrombolyzed a HIT patient with 15K platelets and with massive PE and generally they don't bleed," said Dr Bartholomew, as I imagined him with a cowboy hat planted on his head.
Ahh. . . . With that statement I was firmly in love with this session. I had found my perfect session speed date.
Next, we heard more about how we should test patients who experience their first VTE before age 50 or those with any strong family history or unusual sites such as hepatic, mesenteric, portal, or cerebral veins. We should also test patients with VTE associated with pregnancy or oral contraceptives. We reviewed the correct tests to order—which might be hard for us nonhematologists to remember at 2 am: antithrombin, protein C and S, factor V Leiden, prothrombin mutation G20210A, fasting plasma homocysteine, lupus anticoagulant, and anticardiolipin antibodies IgG, IgM, and beta 2 glycoprotein IgG and IgM were all listed.
Equally as important, he reviewed who not to test for thrombophilia: Those with major surgery, trauma or immobilization, malignancies, inflammatory bowel disease, myeloproliferative disorders, medical illness such as CHF and pneumonia, upper-limb DVTs, and patients with HIT. He reminded us that the presence of active thrombosis can lower the levels of protein C, S, and VIII levels, that heparinized patients can't be tested for lupus anticoagulant, that warfarin produces a false positive in lupus patients, and that warfarin-treated patients cannot be tested for protein C and S. It was emphasized that antiphospholipid antibodies, factor V Leiden assays, and prothombin gene mutations are bulletproof from any influence of acute thrombosis or anticoagulation and so are fair game for testing under nearly any pharmacologic circumstances.
I don't want to leave out Dr Casanegra, who discussed the antiphospholipid syndrome (APS) and how there is a 20% to 30% failure rate of therapy in obstetric cases and that 3% to 9% go on to develop thrombosis on warfarin. She reminded us that the INR is falsely elevated in 10% of APS patients and that hydroxychloroquine and statins are now considered possible treatment options. She noted that the efficacy and safety data for direct oral anticoagulants (DOACs or NOACs) are limited in this setting, with a few case reports of DOAC failure tipping us off that prior arterial and recurrent events are risk factors, as well as "triple positivity" with LA, AcL, and B2GP findings. She then mentioned that we can look forward to future small trials including RAPS (2016), ASTRO-APS (2017), and TRAPS (2018) on the subject.
So that's it. I learned, I loved, and I got lost in all the data, forgetting the time and nearly closing down the pressroom to try to finish this piece. But like so many fickle lovers, tomorrow is another day, and I'll be looking again.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Melissa Walton-Shirley. Hypercoagulable States: On Clots and Other Things - Medscape - Nov 15, 2016.