THROMBOSIS AND THE CLOTTING CASCADE AND YOU William Houck Shenandoah Oncology
WE LL TALK ABOUT Remembering the clotting cascade and the key players Tests for hypercoagulable states & when to do Remembering the drugs to treat hypercoagulable states Some clinical scenarios
BACK TO THE BASICS.
THE CLOTTING CASCADE
OH LORD IT S THE CLOTTING CASCADE.
OH LORD IT S THAT CLOTTING CASCADE AGAIN
NATURAL PROTEINS THAT INHIBIT CLOTTING
WHERE DO WE CLOT? Veins-A)Superficial veins B)Deep Venous System Arteries
DVT VS SVT
CLINICALLY, A SUPERFICIAL CLOT..
WHAT S A DVT LOOK LIKE?
TOOLS TO DIAGNOSE A CLOT? Ultrasound Angiograms(by Ct, MRI, or injection)
ULTRASOUND SHOWING A CLOT
ANGIOGRAM SHOWING A CLOT
SO WE HAVE A CLOT. Anticoagulation: Point of therapy: Reduce risk of extension or a new clot Duration of therapy Risk of treatments? Cause?
SO WHAT CAUSES A BLOOD CLOT? Idiopathic Obesity Smoking Surgery Immobility Cancer Birth Control Pills Mutations of the Proteins that Inhibit Clotting
Mutations: Factor V Leiden-5% Prothrombin Gene-1-2% Reduction in Protective Proteins Proteins s& c THE INHERITED REASONS FOR CLOTTING
WHO SHOULD BE TESTED FOR MUTATIONS? Young(>45 yo) Family History Repeat offenders
RAMIFICATIONS OF THE MUTATIONS Duration of therapy? Family History
FINALLY, SOME TREATMENT TALK Anticoagulate-reduce risk of clot extension or recurrent clot Risks of bleeding
WHAT OUTPATIENT AGENTS COULD WE USE TO KEEP FROM CLOTTING? Coumadin-Interferes with Vitamin k Lovenox DOACs
COUMADIN(WARFARIN) Inhibits Clotting Factor produced by liver, as well as Protein S, C, AT III Risk of hypercoagulable state on initiation due to MOA Follow INR-costs associated with monitoring Innumerable interactions: Diet and Medications Bleeding Risk-1-2% major bleeds per yr, 9% minor bleeds Easily reversible-vitamin K and ffp Cheap
ANOTHER VISUAL FOR HOW COUMADIN WORKS
LOVENOX Shot that blocks factor x and to an extent factor 2 Shot(once a day 1.5 mg/kg or 1 mg/kg bid) Use restricted by Renal Dysfunction 2-3k month SHOT Limited reversibility
HOLY MOSES, SO MANY ANTICOAGULANTS.
DOACS New Kids on the block Many agents-we ll focus on a couple Oral 450 a month Limited Reversibility NO testing needed Bleeding risks less than coumadin
ELIQUIS(APIXABAN) Mild-to-moderate Renal dysfunction: No dosage adjustment required Serum creatinine 1.5 mg/dl: Decrease dose to 2.5 mg BID if patient has 1 additional characteristic of age 80 years or weight 60 kg ESRD maintained on hemodialysis: 5 mg BID; decrease dose to 2.5 mg BID if 1 additional characteristic of age 80 years or weight 60 kg is present Can use if no significant liver dysfunction Discontinue at least 48 hr before elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding Discontinue at least 24 hr before elective surgery or invasive procedures with a low risk of unacceptable or where the bleeding would be noncritical in location and easily controlled Reversal agent(andrexxa) $450 a month
PRADAXA(DABIGATRAN) Converting to parenteral anticoagulant: Wait 12 hours ( CrCl 30 ml/min) or 24 hours (CrCl <30 ml/min) after last dabigatran dose before initiating parenteral anticoagulant If possible, discontinue dabigatran 1 to 2 days (CrCl 50 ml/min) or 3 to 5 days (CrCl <50 ml/min) before invasive or surgical procedures because of the increased risk of bleeding Converting from warfarin: Discontinue warfarin and initiate dabigatran when INR <2.0 Dosing CrCl >30 ml/min: 150 mg PO BID CrCl 30 ml/min or on dialysis: Dosage recommendations cannot be provided $450 a month
XARELTO(RIVAROXABAN) Peak plasma time: 2-4 hr AUC: 29-56% decrease when released in proximal small intestine compared with gastric absorption Half-life: 5-9 hr; 11-13 hr (elderly) Avoid concomitant use of P-gp and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, conivaptan); may increase risk of bleeding Careful in Renal dysfunction Andexxa(reversal agent)
HOW DO YOU PICK Drug Cost Oral vs IV Coexisting Diseases(Lupus Anticoagulant or Cancer)
CONUNDRUMS WITH NOACS Quickly supplanting other options in DVT, PE, and other situations Special Patient Populations:?Lupus anticoagulant or Cancer Patients Obese
Historically hypercoagulable Arterial clots Coumadin Vs DOAC? -Case series like Blood 2017. 130.4917 HOW ABOUT IN APS/LUPUS ANTICOAGULANT
CANCER PATIENT? LMWH vs Coumadin: several studies in early 2000s reduce clotting by half and lower bleeding risk vs coumadin. Defacto use lovenox preferentially DOACs?
Submit in Cancer Patients DOAC IN CANCER?
DOAC IN MORBIDLY OBESE PATIENT?
MORBID OBESITY AND ELIQUIS(BLOOD 2017:130:1105)