Anticoagulants | The Massachusetts General Hospital Handbook of Neurology

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

> Table of Contents > Drugs > Anticoagulants

Anticoagulants

A. Contraindications to anticoagulation (relative)

Large territory brain infarct, brain tumor, cerebral aneurysm, abdominal aortic aneurysm >6 cm, fever/new heart murmur (?septic emboli), thrombocytopenia, SBP >210, recent surgery or trauma, history of cerebral or severe GI bleed, cholesterol emboli.

B. Prevent complications

Consider GI prophylaxis, checking CBCs, stool guaiacs, relevant coagulation parameters (PT, PTT, or anti-Xa).

C. Warfarin (Coumadin)

Goal PT/INR = 2-3 for A fib (unless under 65 with no risk factors), DVT, LV thrombus, antiphospholipid syndrome (see p. 192). Goal is 3-4.5 for mechanical valve. Typical load is 10 mg qd 2 d, then 5 mg qd; decrease this for small or old pts. Overlap with heparin for at least 24 h of therapeutic PT to prevent early paradoxical hypercoagulability. With an INR of 2-3, bleed rate per year is about 2%; 0.6% for cerebral bleed. Concomitant aspirin probably doubles the bleed rate.

Drugs that decrease warfarin clearance, raise PT: Acetaminophen, allopurinol, amiodarone, Bactrim, cimetidine, fluconazole, isoniazid, metronidazole, indomethacin, omeprazole, oral hypoglycemics, phenothiazines, quinidine, salicylates, TCAs.
Drugs that increase warfarin clearance, lower PT: Barbiturates, oral contraceptives, rifampin.
Heparin: Goal PTT = 60-80, except as below. Watch for heparin-induced thrombocytopenia (see p. 193).
- For prophylaxis of DVT: 5000 U SQ bid.
- For rx of stroke, DVT, PE:
  - Boluses: Avoid them in stroke, unless there is brainstem ischemia or a fluctuating neuro exam. Use boluses in PE, MI. Typically 3,000-5,000 U.
  - Initial rate: Typically 1,000 U/h; give 600-800 U/h if pt. small, old, or frail; consider 1,300-1,500 U for big young pts.
  - Sliding scale: For bid PTT:

E. Low molecular weight heparin (LMWH)

Enoxaparin (Lovenox), dalteparin (Fragmin). Fragments of unfractionated heparin. QD dosing, greater bioavailability, longer duration, fixed weight based dosing, no

P.161

need for PTT monitoring or IV. All inactivate factor Xa and have lesser effect on thrombin. Lower risk of HIT. Better than warfarin for DVT prophylaxis in cancer pts and in acute PE.

Table 44. Heparin sliding scale.

PTT	Dose Correction
>120	Stop heparin, recheck PTT superstat in 2 h
100-119	Hold hep. 2 h; decrease 200 U/h, recheck in 4 h
90-99	Decrease 200 U/h
80-89	Decrease 100 U/h
60-79	No change
50-59	Increase 100 U/h
40-49	Increase 200 U/h
40	Bolus 3000 U, increase 200 U/h, recheck stat in 4 h

F. Heparinoids

E.g., danaparoid, fondaparinux (Arixtra). Synthetic heparin-like polysaccharides. They bind antithrombin III and thus inhibit factor Xa. Use instead of IV heparin if pt. has heparin-induced thrombocytopenia (see p. 193).

Danaparoid (Orgaran): A heparinoid. Bolus 1,250-2,000 U, then 400 U/h for 4 h, then 300 U/h for 4 h, then 150 U/h. After a few hours on 150 U/h, draw danaparoid level and anti-Xa level; use these to adjust danaparoid rate. Kidney elimination.

G. Direct thrombin inhibitors

All used as anticoagulants in patients with heparin-induced thrombocytopenia (HIT; see p. 193). They are hard to monitor and have no specific antidotes.

Lepirudin and hirudin: Contraindicated in renal failure.
Argatroban: Contraindicated in liver failure. It interferes with INR measurements, so switching to coumadin is complicated.
Ximelagatran: The single oral alternative to warfarin.

H. Reversing anticoagulation

Contraindications: Prosthetic valve, basilar thrombosis, etc.
Warfarin: Vitamin K 1 mg IV/SQ to lower PT a little. 10 mg qd 3 d normalizes it but makes anticoagulation hard for the next week.
Heparin: Protamine 10-50 mg IV over 5 min. 1 mg reverses approximately 100 U of heparin.
Others: If active bleeding, consider fresh frozen plasma; DDAVP to boost platelets.