Cardiac and Vascular Dept. John Paul II Hospital Kraków, Poland

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1 Leśniak-Sobelga Agata, Drabik Leszek, Wiśniowska-Śmiałek Sylwia, Kostkiewicz Magdalena, Undas Anetta, Rytlewski Krzysztof, Huras Hubert, Stettner Dominika, Wilkosz Tadeusz, Podolec Piotr Cardiac and Vascular Dept. John Paul II Hospital Kraków, Poland

2 A 31-y-old obese woman had been diagnosed with distal deep vein thromboembolism (DVT) at age 18. Her first pregnancy at age 28 was uneventful. In week 10 of her second pregnancy she was diagnosed with left iliofemoral DVT; treated with unfractionated heparin (UFH) for 3 days and enoxaparin 100 mg twice daily for 32 days. In week 16 the patient complained of dyspnea, cough and chest pain. Physical examination revealed no hypotension and cyanosis.

3 Deep vein thromboembolism (DVT) is one of the most common causes of death among women in the perinatal period and the puerperium. The rate of occurrence of DVT in pregnancy is approximately per 1000 women, and the most common locations are the lower limbs and the deep veins of the pelvis. Low-molecular-weight heparins (LMWH) are medications of choice if DVT is found in pregnancy.

4 BMI 30.9 kg/m 2, BP 134/82 mmhg. Lower limbs were tender, warm and swollen, without skin lesions. Laboratory exams revealed marked thrombocytopenia 38x10 3 /µl (a drop from an initial value of 337 x 10 3 /µl), high D-dimer 3959 ng/ml [N: <500], normal activated partial thromboplastin and prothrombin time. Due to high clinical probability of HIT, LMWH was discontinued and treatment with fondaparinux 7.5 mg s.c. once daily begun.

5 The following features support a diagnosis of HIT-II: a drop in platelet count 50%, from highest platelet count after heparin exposure; nadir platelet count 20x10 9 /L in cases associated with thrombosis and disseminated intravascular coagulation; venous or arterial thrombosis occurring 5 days after heparin exposure and up to 30 days after cessation; skin necrosis at subcutaneous heparin injection sites; anaphylactoid reaction within 30 minutes after iv heparin bolus; absence of alternative causes of thrombocytopenia; absence of petechiae and other significant bleeding

6 Two weeks later (while still on Fondaparinux) the inferior vena cava (IVC) up to the level of renal veins and bilateral iliofemoral veins were extensively occluded. Laboratory tests showed high CRP 194; 23 mg/l, D-dimer 2301 ng/ml, mild normocytic anemia; normal platelet count 282x10 3. Antibodies against platelet factor 4/heparin (GTI Diagnostics PF4 IgG) were highly elevated (2.8 and 3.0 OD [>0.400 positive]), confirming the diagnosis of HIT.

7 The occlusion of right common iliac vein The occlusion of vena cava inferior

8 Thrombophilia screening showed: normal antithrombin (115%), protein C (123%) and protein S (72.6%). factor VIII was moderately elevated -211% (50-150) fibrinogen level was elevated (8.56 g/l) antibodies IgG anti-beta2-glicoprotein and IgM anti-beta2-glicoprotein were normal (relatively, 0.3 SGU and 1.0 SMU [ ]) lupus anticoagulant level was mildly elevated (N <1.2) the heterozygotic form of factor V Leiden was detected.

9 Transthoracic echocardiography showed normal cardiac chamber dimensions, preserved biventricular systolic function, no evidence of thrombus, and no signs of pulmonary hypertension. An electrocardiogram showed a sinus rhythm with a heart rate of 90 bpm. Holter monitoring revealed no severe arrhythmia. The patient was treated with fondaparinux during the next 10 days (total ~24 days), and subsequently with warfarin monitored against target INR 3.0.

10 Serial utrasound exams showed no further progression of vein thrombosis, and slow regression began. The condition of the fetus was normal. Uterine and umbilical artery Doppler assessments were normal. After 3 uneventful weeks, the patient was discharged.

11 During week 24 of pregnancy, she was admitted to the Dept. of Obstetrics and Perinatology due to missed abortion. On the 3 rd day, due to decreasing value of INR-1.5, labour was induced, with Misoprostol administration to the posterior fornix of the vagina: two doses (0.2 mg) with 4h interval. A dead male foetus (860 g) was delivered preterm. The patient was discharged on the 4 th day after delivery. A bearing test showed diffuse infiltration of neutrophils. The specimens were small areas of necrosis surrounded by deposits of fibrin.

12 7 months after delivery, antibodies against platelet factor 4/heparin were still elevated (2.3 OD), D-dimers and fibrinogen were within normal limits; lupus anticoagulant level (1.7) and factor VIII were elevated (217%), and ANA-1 were negative.

13 Due to elevated level of the antibodies against platelet factor 4/heparin, heparin treatment should be avoided in this patient.

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