Protein C plays a key role in the regulation of hemostasis, and its deficiency is associated with an increased risk of thromboembolism. Protein C-deficient women are at particular risk of developing thromboembolic complications during antenatal period and delivery. The incidence of thromboembolic events is estimated to be 1000 times higher than in normal women. We report the case of a 28-year-old woman with cortical vein thrombosis, who experienced a successful pregnancy and delivery despite protein C deficiency. She was anticoagulated with heparin during the second part of her pregnancy. Our observation suggests that ambulatory full-dose subcutaneous LMWH therapy during pregnancy constitutes adequate prevention. However, definite guidelines are still under making.

CASE REPORT

A G3P1L0A1 in her 20’s came to us in emergency with complain of tingling sensation in left upper limb, deviation of angle of mouth towards left with salivation for 5-10 min and uprooting of eye balls, vomiting 2-3 episodes at home after confirmation of pregnancy. On evaluation she was diagnosed with Protein C deficiency. Patient had history of one full term normal vaginal delivery (baby certified at 1.5 month of delivery) and one spontaneous abortion of 1.5 months not followed by D and C.

Her Investigation were: Hemoglobin - 10.5 gm/dl, Platelet count - 2.2 lakh, PT / INR - 0.92, aPTT - 28.9

Fibrinogen level - 239.8 (normal)D-dimer - 0.89 (raised)

Homocysteine 12.43 mmol/l (normal)Antithrombin 3- normal

Anticardiolipin IgM, IgG Negative

Anti phospholipid antibodies IgM IgG negative Protein C - 630.5 Units(decreased)

Protein S - 1.89 ng/ml (normal)

In the present pregnancy, she was admitted and started on Inj enoxaparin . No bleeding complication occurred during third trimester. A multidisciplinary team comprising obstetrician, haematologist, physician were involved in management. At term, patient was induced for labour. She delivered a male baby 2.7 kg, alive and healthy with no intra and post partum bleeding manifestation.

No PPH or any haemorrhagic event occurred. DVT prophylaxis was given with DVT stockings, early ambulation and hydration.

No haemorrhagic complications were reported for neonate also.

Patient was followed for 6 weeks post-partum visit and 6 months post-delivery. Lactation was established and her periods resumed after 6 months. There were no haemorrhagic complications in both mother and baby.

DISCUSSION

Proteins C and S are vitamin K-dependent plasma proteins that work as an important part of the body’s anticoagulant system. They act through the selective inactivation of Factors Va and VIIIa. Mutations in protein C and S genes are the main cause for their deficiencies. Pregnancy is a hypercoagulable state. Normal pregnancy is associated with increased procoagulants and decreased fibrinolysis to maintain placental hemostasis during pregnancy. However, hypercoagulability due to deficiency of any antithrombotic factors leads to placental hypoperfusion, thrombosis, fetal growth retardation, fetal demise. Protein S deficiency is more common than protein C deficiency, constituting an increased risk of recurrent pregnancy loss. Therefore, thrombophilia screening is indicated in women who have recurrent pregnancy loss. Management of Protien C deficiency is low molecular weight heparin (LMWH) during antenatal and postnatal period.

CONCLUSION

Physiological changes in pregnancy create a procoagulant state with increased chances of blood loss during delivery. Deficiency in any of the factors in coagulation cascade can lead to catastrophic haemorrhage.

Multidisciplinary team approach will help in improving outcomes in these women, with rare life threatening condition. Delivery plan should be made and executed with proper monitoring.

CASE TWO

Normal pregnancy is accompanied by state of hypercoagulablility. The most important risk factors are history of thrombosis and thrombophilia. Most thrombosis in pregnancy occur in the left lower limb, but pelvic vein thrombosis are also common. Thrombophilia also increases the risk of maternal thrombosis .All pregnant women should be asked about a personal or family history of thrombosis and obstetrical history. Therefore screening during antenatal visits is important, particularly those with history of thrombosis or a history of pregnancyloss. The purpose of screening is to help determine which women should receive anticoagulation therapy, so as to prevent thromboembolism and reduce the risk of poor pregnancy outcome. Low-molecular-weight heparins are preferred over unfractionated heparin because they have a longer half-life and are have fewer side effects. The risk of thrombosis is higher in postpartum period than during antenatal period, so anticoagulation therapy is usually continued for at least 6 weeks post delivery.

CASE REPORT

A P1L0 20 yrs of age, came to us with lower limb swelling since 8 days, on post LSCS day 20. She was operated for antepartum eclampsia . Patient was not screened during antenatal visits. She was a referred patient from periphery. On pre-operative work-up her INR was 1.3. Intra-operative and post-operative periods were uneventful and no haemorrhagic event was reported.

In the present pregnancy, she presented to us with GTCS seizures at home. No bleeding complication occurred during first and second trimester. A multidisciplinary team comprising obstetrician, haematologist, physician, anaesthetist and neonatologist were involved in management. At 32 weeks, plan for emergency caesarean section was made in view of antepartum eclampsia. She had pedal oedema 2+ after delivery, which subsided till discharge. Intra-operative and post-operative period were uneventful. No PPH or any haemorrhagic event occurred. DVT prophylaxis was given with DVT stockings, early ambulation, thromboprophylaxis with low molecular weight heparin and hydration. Patient was discharged on day 7 with controlled BP.

In post-operative period, oedema increased at postoperative day 12. On Dopplerscan (lower limb): Thromboses right common femoral, superficial femoral and popliteal vein and left common femoral vein; Partially thrombosed left superficial common femoral vein; Diffuse subcutaneous edema in lower limbs was seen.

On work up : Hemoglobin 9 gm Platelet count 1.5 lakh

PT / INR 1.40

aPTT 18.6 (mildly raised)

Serum Calcium 8.32(mildly decreased)Fibrinogen level 2.99 g/L

D-dimer <0.22 ng/ml

ESR 41 (raised)

Lupus anticoagulant 41.60 sec (normal) Homocysteine 16.13 (mildly raised)ANA Negative

IgM Beta 2 Glycoprotein 32.50 (positive)

On haematological opinion: Thromboprophylaxis with Tab Rivaroxaban 15mgwas started with follow up lower limb doppler.

Patient was followed for 6 weeks post-partum visit and 6 months post-delivery. Lactation was established and her periods resumed after 6 months. There were no haemorrhagic complications in both mother and baby. Implanon subdermal implant device was placed for contraception.

DISCUSSION

The incidence of venous thromboembolism (DVT and pulmonary embolism [PE])increases in pregnant women. The three main contributing factors-hypercoagulability , stasis and endothelial injury. Patients usually present with symptoms like leg pain and shortness of breath, making clinical diagnosis difficult. Also in patients with acute venous thromboembolism, the prevalence of antibodies against beta2GPI is unexpectedly high. The presence of these antibodies identifies a sub group of patients with anti-phospholipid antibodies who have a specifically high risk of thrombotic recurrences. Low molecular weight heparins are typically the drug of choice for prophylaxis and treatment of VTE in pregnant women.

CONCLUSION

The successful management—transitioning from prophylactic to therapeutic anticoagulation with Rivaroxaban—and the favourable maternal and neonatal outcomes at six-month follow-up emphasize the need for a high index of suspicion for venous thromboembolism in the peripartum period. Furthermore, it reinforces that standard prophylactic regimens may be insufficient for individuals with identified thrombophilia.

In conclusion, a proactive approach involving risk assessment, timely screening, and individualized thromboprophylaxis is paramount to mitigate the significant morbidity associated with venous thromboembolism in pregnancy and the puerperium.

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