Initial treatment for confirmed VTE

a. Heparin or Fondaparinux and vitamin K antagonists (VKA)b. Rivaroxaban
Rivaroxaban is indicated for the treatment of acute deep vein thrombosis and pulmonary embolism and the prevention of recurrenceNotes on Initial treatment
In clinically suspected cases with high probability VTE, treatment with LMWH or fondaparinux should be given until the diagnosis is excluded by objective testing. In patients with confirmed DVT or PE, offer a choice of LMWH, fondaparinux or rivaroxaban, taking into account comorbidities, contraindications and drug costs. Start treatment as soon as possible.Adequate analegesia should be given and the leg elevated.

Offer warfarin within 24 hours of diagnosis in combination with LMWH or fondaparinux. For rivaroxaban, no overlap with LMWH or fondaparinux is needed as rivaroxaban has a rapid onset of action and predictable bioavailability. In patients with severe renal impairment or established renal failure (eGFR <30 ml/min) offer UFH with dose adjustments based on APTT or LMWH with dose adjustments based on anti-Xa assay.For patients with PE and hemodynamic instability, offer iv UFH and consider systemic thrombolytic therapy.

Low molecular weight heparin
Low molecular weight heparin is associated with decreased mortality, lower recurrence of VTE and decreased incidence of major bleeding when compared with unfractionated heparin. It does not require monitoring and it's ease of use makes outpatient treatment feasible.
Currently available LMWHs in Malaysia and recommended doses for the treatment of acute VTE are as shown in the Table

LMWHs and the recommended doses for the treatment of acute VTE

LMWH

Treatment dose

Enoxaparin
(20, 40, and 60 mg prefilled syringes)
1 mg/kg twice daily
Tinzaparin
(0.5 and 0.7 mL of 20,000 anti-Xa IU/mL prefilled syringes)
175 units/kg once daily
A simple way to calculate tinzaparin dose: Volume of tinzaparin in mL required = (weight in Kg - 10) ÷ 100
e.g. 60 kg patient = 0.5 mL; 70 kg = 0.6 mL; 45 kg = 0.35 mL tinzaparin)


Fondaparinux
Fondaparinux is an indirect inhibitor of activated factor X. It does not inhibit thrombin and has no effect on platelets. It is given subcutaneously and the dosing for the treatment of VTE is based on the body weight. Fondaparinux must be used with caution in patients with renal impairment as it is eliminated unchanged in the kidneys. Fondaparinux, like LMWH is continued for at least 5 days or until the INR is above 2 for at least 24 hours, whichever is longer.

The recommended doses for fondaparinux in the treatment of acute VTE
Body weight, kgDosing, mg
< 505
50 - 1007.5
>10010


Rivaroxaban
Rivaroxaban is a highly selective, direct factor Xa inhibitor that is orally active with a rapid onset of action. The dose used in the treatment of VTE is 15 mg twice a day as the loading dose for 3 weeks followed by 20 mg daily. At these doses, it has been shown to be non-inferior to enoxaparin followed by warfarin with significantly less major bleeding complications.

Switching heparin to rivaroxaban
For patients currently receiving a parenteral anticoagulant, rivaroxaban should be started 0 to 2 hours before the time of the next scheduled administration of LMWH or at the time of discontinuation of continuous intravenous unfractionated heparin.

Switching rivaroxaban to heparin
To convert rivaroxaban to LMWH, give the first dose of LMWH at the time the next rivaroxaban dose would be taken or 12 hours after the last dose of rivaroxaban.

Switching VKAs to rivaroxaban
Stop VKA and allow INR to fall. Rivaroxaban can be given as soon as INR ≤ 2.5.

Switching rivaroxaban to VKA
There is a potential for inadequate anticoagulation during the transition from rivaroxaban to VKA. Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that rivaroxaban can contribute to an elevated INR. In patients converting from rivaroxaban to VKA, VKA should be given concurrently until the INR is ≥ 2.0. For the first 2 days of the conversion period, standard initial dosing of VKA should be used followed by VKA dosing guided by INR testing. While patients are on both rivaroxaban and VKA, the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of rivaroxaban. Once rivaroxaban is discontinued, INR testing may be done reliably at least 24 hours after the last dose.

Dabigatran
At the time of writing this cpg, dabigatran is not licensed for use in the treatment of VTE.

Intravenous unfractionated heparin
Intravenous UFH is no longer the standard treatment in DVT and PE because it has to be given as an infusion with frequent APTT monitoring and may take more than 12 hours to achieve therapeutic level. All patients receiving UFH should have a platelet count performed at baseline but do not necessitate platelet count monitoring unless post-operative.The duration of initial iv UFH therapy in patients with VTE is between 5 to 7 days. To standardize the management of iv UFH, a weight-based normogram is used:

Management with IV UFH
Initial dose80 IU/kg bolus, then 18 IU/kg/h
APTT ratioAction and Dose changeNext APTT
<1.2 (APTT <35s)80 IU/kg bolus, then increase rate by 4 IU/kg/h6 h
1.2 - 1.5 (APTT 35 to 45s)40 IU/kg bolus, then increase infusion rate by 2 IU/kg/h6 h
1.5 - 2.5 (APTT 46 to 70s)No change24 h
2.5 - 3.0 (APTT 71 to 90s)Decrease infusion rate by 2 IU/kg/h6 h
>3.0 (APTT >90s)Withold infusion for 1 hour, then decrease infusion rate by 3 IU/kg/h6 h