THROMBOSIS AND THE CLOTTING CASCADE AND YOU. William Houck Shenandoah Oncology

Transcription

1 THROMBOSIS AND THE CLOTTING CASCADE AND YOU William Houck Shenandoah Oncology

2 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

3 BACK TO THE BASICS.

4 THE CLOTTING CASCADE

5 OH LORD IT S THE CLOTTING CASCADE.

6 OH LORD IT S THAT CLOTTING CASCADE AGAIN

7 NATURAL PROTEINS THAT INHIBIT CLOTTING

8 WHERE DO WE CLOT? Veins-A)Superficial veins B)Deep Venous System Arteries

9 DVT VS SVT

10 CLINICALLY, A SUPERFICIAL CLOT..

11 WHAT S A DVT LOOK LIKE?

12 TOOLS TO DIAGNOSE A CLOT? Ultrasound Angiograms(by Ct, MRI, or injection)

13 ULTRASOUND SHOWING A CLOT

14 ANGIOGRAM SHOWING A CLOT

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16 SO WE HAVE A CLOT. Anticoagulation: Point of therapy: Reduce risk of extension or a new clot Duration of therapy Risk of treatments? Cause?

17 SO WHAT CAUSES A BLOOD CLOT? Idiopathic Obesity Smoking Surgery Immobility Cancer Birth Control Pills Mutations of the Proteins that Inhibit Clotting

18 Mutations: Factor V Leiden-5% Prothrombin Gene-1-2% Reduction in Protective Proteins Proteins s& c THE INHERITED REASONS FOR CLOTTING

19 WHO SHOULD BE TESTED FOR MUTATIONS? Young(>45 yo) Family History Repeat offenders

20 RAMIFICATIONS OF THE MUTATIONS Duration of therapy? Family History

21 FINALLY, SOME TREATMENT TALK Anticoagulate-reduce risk of clot extension or recurrent clot Risks of bleeding

22 WHAT OUTPATIENT AGENTS COULD WE USE TO KEEP FROM CLOTTING? Coumadin-Interferes with Vitamin k Lovenox DOACs

23 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

24 ANOTHER VISUAL FOR HOW COUMADIN WORKS

25 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

26 HOLY MOSES, SO MANY ANTICOAGULANTS.

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28 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

29 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

30 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

31 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; 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)

32 HOW DO YOU PICK Drug Cost Oral vs IV Coexisting Diseases(Lupus Anticoagulant or Cancer)

33 CONUNDRUMS WITH NOACS Quickly supplanting other options in DVT, PE, and other situations Special Patient Populations:?Lupus anticoagulant or Cancer Patients Obese

34 Historically hypercoagulable Arterial clots Coumadin Vs DOAC? -Case series like Blood HOW ABOUT IN APS/LUPUS ANTICOAGULANT

35 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?

36 Submit in Cancer Patients DOAC IN CANCER?

37 DOAC IN MORBIDLY OBESE PATIENT?

38 MORBID OBESITY AND ELIQUIS(BLOOD 2017:130:1105)