Rheological, hemostaseological changes during immunetherapy for prevention of HELLP-syndrome in a patient with elevated phospholipid antibodies

Article type: Research Article

Authors: von Tempelhoff, Georg-Friedrich^{a; b; *} | Tsikouras, Panagiotis^{a; d} | Rath, Werner^e | Velten, Eva^{a; b} | Csorba, Roland^{a; b; c}

Affiliations: [a] Department of Obstetrics and Gynecology, City Hospital of Aschaffenburg, Aschaffenburg, Germany | [b] Institut of Coagulation Disorders in Obstetrics and Gynecology, Freiherr vom Stein, Hausen, Germany | [c] Department of Obstetrics and Gynaecology, University of Debrecen, Hungary | [d] Democritus University of Thrace, Department of Obstetrics and Gynecology, Alexandroupolis, Greece | [e] Department of Obstetrics and Gynecology, University RWTH Aachen, Aachen, Germany

Correspondence: [*] Corresponding author: Georg-Friedrich von Tempelhoff, Institute of Coagulation Disorders in Obstetrics and Gynecology, Freiherr vom Stein Str.29, 63179 Hausen, Germany. Tel.: +49 14221 554988; Fax: +49 6106 610682; [email protected]

Abstract: OBJECTIVE: Patients with a history of severe obstetric complications in the presence of elevated phospholipid antibodies are at high risk for recurrent obstetric debacle. We report a successful immunologic treatment for prevention of HELLP-Syndrome in subsequent pregnancy in a patient with elevated Phospholipid antibodies, while under rheological and hemostaseological monitoring. METHODS: The patient with prior severe HELLP-Syndrome at term in the presence of reconfirmed elevated phospholipid antibodies in her first pregnancy received pooled immunoglobulins (Sandoglobulin 3 g - Novartis) intravenously for immunological treatment every three weeks in addition to low molecular weight heparin (Clexane 40 mg/d s.c.) and Aspirin (100 mg/d from 2nd trimester) during her subsequent pregnancy. Before each of 10 treatment cycles blood rheological parameters (Red Blood cell {RBC} aggregation stasis E0, low shear E1, RBC - deformability low-, moderate-, and high shear force, plasma viscosity {Pv}), as well as thrombelastometry (ROTEM) and in vitro platelet function (PFA-100) for hemostaseological evaluation was performed. At the same times non-invasive, physical thrombosis screening took place using impedance plethysmography (Filtrass) RESULTS: During pregnancy a constant increase in PV and E1 (>45 S −1) was accompanied by a delayed but continuous increase in RBC deformability beginning at the end of the 2nd trimester. Thrombelastometry revealed a continuous reduction of clot formation time (CFT; extem: 84 to 38 sec) and an increase in maximal clot firmness (MCF; extem: 64 to 78 sec) after TF-induced coagulation activation while MCF and CFT after contact activation (intem) was barely unchanged. Platelet bleeding-time after EPI/Coll stimulation was temporary prolonged by the onset of Aspirin intake (>300 sec) but normalized soon after 20th gestational week, while ADP/Coll stimulation revealed a trend towards prolonged bleeding times at the same time. There was a strong and statistically significant inverse correlation between E1 and TF induced CFT (r =−0.82; p = 0.002) and a positive correlation between E1 and TF induced MCF (r = 0.89; p <  0.001), while the correlation between E1 and contact activated CFT and MCF was weak or absent, respectively. Until GW 38th routine laboratory- (Platelet-count, Haptoglobin, liver enzymes) and clinical findings remained normal, without evidence of HELLP-Syndrome reoccurrence or development of thrombosis. CONCLUSIONS: During immunotherapy in this high risk patient HELLP-Syndrome did not reoccur. The aggregability of RBC was closely related with the formation speed and firmness of clot after TF activated coagulation but not after contact activated coagulation. At the beginning of 3rd trimester RBC aggregation remained dramatically higher as compared to the normal value range of pregnant women found in a large recent trial which may have been an early indicator of imminent HELLP-Syndrome.

Keywords: Pregnancy, antiphospholipid syndrome, HELLP syndrome, plasma viscosity, red blood cell aggregation, immunological treatment, thrombelastometry, platelet function

DOI: 10.3233/CH-151937

Journal: Clinical Hemorheology and Microcirculation, vol. 60, no. 1, pp. 123-131, 2015