Choice of anticoagulants in DVT in pregnancy
In pregnancy, Virchow’s triad, composed of hypercoagulability, stasis and endothelial injury are 5 times more likely to occur when compared to normal non pregnant females. During pregnancy, blood volume increases, blood velocity decreases and diameter of the blood vessels increases in the major leg veins. Hence, the clotting/coagulation factors such as II, VII, VIII, X are triggered resulting in thrombus formation especially in the lower extremities of the body. Fall in the levels of protein S and resistance to protein C are noticed. This results in deep vein thrombosis or DVT which left untreated leads to pulmonary embolism sooner or later after delivery. A reduction in venous flow velocity occurs in the legs by weeks 25–29 of gestation. This lasts until approximately 6 weeks postpartum, at which time normal venous velocities return.
The definitive diagnosis of DVT is done using ECHO, ECG, Chest X-ray, Coronary artery and venous doppler studies. Initiation of therapy using D-dimer test results will be misleading since hypercoagulability is normal in pregnancy.
Therapeutic options available for DVT:
The following are the list of anticoagulants that are commonly used in the treatment of DVT.
Low molecular weight heparin (Enoxaparin, Dalteparin, Tinzaparin)
Factor Xa inhibitors (indirect) – Fondaparinux
Direct thrombin inhibitors (Hirudin)
Direct oral anticoagulants (Warfarin, Rivaroxaban, Dabigatran, Apixaban, Edoxaban etc.)
Thrombolytic agents (Streptokinase, Alteplase, Reteplase)
Among the anticoagulants that are commonly used for DVT as given above, choice of anticoagulants must be considered carefully in pregnancy. Among various anticoagulants which are available, unfractionated heparin and low molecular weight heparins are the drug of choice in pregnancy.
This is because,
Low molecular weight heparins are the safest and has minimal risk of heparin induced thrombocytopenia/ maternal bleeding. These are the 1stline agents of choice because they do not cross the placental barrier and result in live foetal births. Low molecular weight heparin must be discontinued 12 hours before delivery to prevent postpartum haemorrhage.
It is available as prefilled injection in the following concentrations,
20mg in 0.2ml given q 12 hours
40mg in 0.4ml given q 12 hours
60mg in 0.6ml given q 12 hours
80mg in 0.8ml given q 12 hours
Based on body weight,
<49.5 kg - 20mg SC daily.
>90 kg - 40mg SC BD (q 12 hour).
50-90 kg – 40mg SC BD.
90-109kg - 100 mg twice daily or 150 mg once daily
110-125kg - 120 mg twice daily or 180 mg once daily
Based on body weight,
<50kg – 5000 IU twice daily or 10 000 IU once daily
50-69kg – 6000 IU twice daily or 12 000 IU once daily
70 -89kg – 8000 IU twice daily or 16 000 IU once daily
90-109kg – 10000 IU twice daily or 20 000 IU once daily
110-125kg - 12000 IU twice daily or 24 000 IU daily
100 units/ kg every 12 hours
200 units/ kg once daily.
The dose needs to be reduced in patients with Crcl <30ml/min.
· 175 units/kg once daily (in early pregnancy)
Dosage adjustment must be made when Crcl is 20ml/min.
Weight-based dosing nomograms have been suggested as an alternative to empiric dosing of UFH for therapeutic anticoagulation.
This results in rapid anticoagulation, allowing for finer adjustments to reach goal activated partial thromboplastin time (aPTT) values. It is most commonly preferred during massive and life threatening pulmonary embolism.
· 5000 IU BD/TDS.
Initially 5000 IU as loading dose followed by continuous infusion of 10,000 IU q 8hrs or 20,000 IU q 12 hours.
1st trimester – 5000 IU SC twice
2nd trimester – 7500 IU SC twice
3rd trimester – 10,000 IU SC twice
ROLE OF INFERIOR VENACAVA FILTERS IN PREGNANCY:
Placement of a temporary inferior vena cava (IVC) filter in obstetric practice is indicated when recurrent thromboembolism occurs despite adequate anticoagulation, or when anticoagulation is contraindicated (such as the peripartum period).
NEWER ANTICOAGULANTS IN PREGNANCY:
These include fondaparinux, argatroban and hirudin. These agents are used where heparin induced thrombocytopenia and skin allergy following heparin administration is encountered.
<50kg – 5mg OD
50-100kg – 7.5mg OD
>100kg – 10 mg OD
The treatment should be continued for a period of 3 to 6 months during pregnancy.
ARGATROBAN AND HIRUDIN:
No reports have suggested the safety concerns of Argatroban and Hirudin in the treatment of DVT in pregnancy.
THROMBOLYTICS IN PREGNANCY:
PCDT is avoided during foetal organogenesis (first trimester) due to the risks associated with radiation exposure. In such situations, the option of termination of pregnancy should be considered. During the second and third trimesters, PCDT should be performed for threatened life or limb and can be considered for failure of conservative management. There are no clear and complete studies performed on thrombolytics in the management of DVT in pregnancy. However thrombolytics must be used with caution in pregnancy only if the benefits outweighs the risk.
NOACs (APIXABAN, RIVAROXABAN, WARFARIN AND DABIGATRAN):
These agents are not preferred in pregnancy due to proven risk of foetal damage as they pass through the placental barrier resulting in foetal loss/haemorrhage.
Danaparoid is generally not recommended for use in pregnancy unless medically necessary or when patients do not respond to 1stline agents in the management of DVT in pregnancy.
Hence, choice of appropriate anticoagulants in pregnancy will reduce the risk of miscarriage/ foetal loss and increases the likelihood of live foetal births.