Antiphospholipid antibodies in convalescent plasma of donors recovered from mild COVID-19 infection.

BACKGROUND AND OBJECTIVES: Passive immunization by the infusion of convalescent plasma (CP) obtained from patients who have recently recovered from COVID-19, thus having antibodies to severe acute respiratory syndrome coronavirus 2, is a potential strategy to reduce the severity of illness. A high prevalence of antiphospholipid antibodies (APLA) in patients with COVID-19 has been reported during the pandemic, raising a concern whether the use of CP could increase the risk of thrombosis in transfused patients. We aimed to evaluate the prevalence of APLA in COVID-19 CP (CCP) in order to assess the potential prothrombotic influence of transfused CCP to COVID-19 patients. MATERIALS AND METHODS: We studied the prevalence of APLA in 122 CCP samples collected from healthy donors who recovered from mild-COVID-19 at two time periods: September 2020-January 2021 (defined as 'early period' samples) and April-May 2021 (defined as 'late period' samples). Thirty-four healthy subjects unexposed to COVID-19 were used as controls. RESULTS: APLA were present in 7 of 122 (6%) CCP samples. One donor had anti-ß2-glycoprotein 1(anti-ß2GP1) IgG, one had anti-ß2GP1 IgM and five had lupus anticoagulant (LAC) using silica clotting time (SCT), all in 'late period' donors. In the control group, one subject had anti-ß2GP1 IgG, two had LAC using dilute Russell viper venom time (dRVVT) and four had LAC SCT (both LAC SCT and LAC dRVVT in one subject). CONCLUSION: The low prevalence of APLA in CCP donors reassures the safety of CCP administration to patients with severe COVID-19.

International Normalized Ratio as a Screening Test for Assessment of Anticoagulant Activity for Patients Treated With Rivaroxaban or Apixaban: A Pilot Study.

Introduction: In patients treated with direct oral anti activated factor X (anti-FXa) anticoagulants such as apixaban and rivaroxaban, there are several emergency and non-emergency conditions in which anticoagulation activity should be measured. The validity of the common global clotting tests, prothrombin time and international normalized ratio (PT/INR) for determination of blood levels of these drugs, has been widely investigated. As the anticoagulation activity evaluation "calibrated anti-FXa" of these drugs is relatively more expensive and less available, we aimed to build a prediction model for anticoagulation activity assessment based on INR values. Methods and Findings: One hundred sixty samples from 80 hospitalized patients treated with apixaban or rivaroxaban were tested using PT/INR and Anti-FXa chromogenic assay. Two blood samples, trough and peak, were collected from each subject. Participants were randomly divided into two equal groups. One group (n = 40) was used to build the model, which was validated by the second group (n = 40). There was a strong correlation between anti-FXa concentrations and INR in rivaroxaban treated patients (r = 0.899, p < 0.001). Therefore, we were able to build a formula for rivaroxaban patient group which reliably represent the relationship between these two parameters. The correlation in apixaban treated patients was less predictive (r = 0.798, p < 0.001) and the formula suggested could not be validated. Conclusions: In our study, we developed a formula that estimates the anticoagulant activity of rivaroxaban by obtaining INR values. Where anti-FXa assay is unavailable, our proposed formula may be considered as a screening test for rivaroxaban.

Platelet distribution width: a novel prognostic marker in an internal medicine ward.

Background: Platelet distribution width (PDW) has demonstrated clinical significance in populations with specific disorders; its prognostic significance in internal medicine wards has not been investigated. Methods: Demographic, clinical and laboratory data were collected prospectively for 1036 internal medicine inpatients. The primary outcome was 90-day mortality, secondary outcomes were: treatment with mechanical ventilation, prolonged hospital stay, in-hospital death, and all-cause mortality following discharge. Data were assessed according to PDW values on admission ≤16.7% (group A) and >16.7% (group B). Results: Compared to group A patients (n = 273), group B patients (n = 763) were more likely to be older, admitted for cardio-cerebrovascular disorder, to present with comorbidities, to be mechanically ventilated, to have prolonged hospital stay and to die during the current hospitalization. The respective 90-day and total (median follow-up of 5 months) mortality rates were significantly higher in group B (13.2% and 16.3%) than in group A (6.6% and 9.5%), P < 0.01. On multivariate analysis, higher PDW values on admission predicted 90-day mortality and shortened survival (relative risks 1.58 and 1.26; 95% confidence intervals 0.89 - 2.78 and 0.97-1.64, respectively). Conclusion: Higher PDW values on admission to internal medicine wards are associated with a more severe clinical profile and increased risk of 90-day mortality.

The proliferation arrest of primary tumor cells out-of-niche is associated with widespread downregulation of mitotic and transcriptional genes.

In recording the changes acquired in gene expression profile during culture of fresh bone marrow samples from patients with multiple myeloma or acute myeloid leukemia, the most remarkable finding in both instances was widespread downregulation of mitotic and transcriptional genes (e.g. MKI67, CCNB1, ASPM, SGOL1, DLGAP5, CENPF, BUB1, KIF23, KIF18a, KIF11, KIF14, KIF4, NUF2, KIF1, AE2FB, TOP2A, NCAPG, TTK, CDC20, and AURKB), which could account for the ensuing proliferation arrest. Many of these genes were also underexpressed in leukemic cells from the blood or myeloma cells from an extramedullary site compared with their expression in the aspirates. Taken together, our results exhibited mitotic and transcriptional gene subsets where their expression appears to be coordinated and niche dependent. In addition, the genes induced during culture specified a variety of angiogenic factors (e.g. interleukin-8 and CXCL-5) and extracellular matrix proteins (e.g. osteopontin and fibronectin) probably released by the tumor cells while generating their favored microenvironment.

GPRC5D is a promising marker for monitoring the tumor load and to target multiple myeloma cells.

In a comparison of gene expression profile in unsorted bone marrow (BM) samples from patients with multiple myeloma (MM), acute leukemia, and diffuse large B-cell lymphoma infiltrating the BM, the leading myeloma distinguishing gene was GPRC5D. This gene was highly expressed in BM samples from the 10 MM cases examined as opposed to minimal expression in samples from the eight cases with other hematological malignancies. Moreover, following antimyeloma treatment the expression of GPRC5D decreased several folds. The strong and selective expression of GPRC5D in MM cells makes this gene and its encoded surface protein as promising markers for monitoring the tumor load and hopefully also as targets for antimyeloma antibodies.

[Laboratory evaluation of lupus anticoagulant in Israel].

Lupus anticoagulants (LAC) are antibodies which are detected by a prolongation of phospholipid-dependent coagulation assays, and are associated with thrombotic events and pregnancy complications in patients with the antiphospholipid syndrome. The antiphospholipid syndrome is defined by arterial or venous thrombosis and/or pregnancy morbidity and by laboratory diagnosis of antiphospholipid antibodies. The laboratory diagnosis is based on LAC and/or anticardiolipin and/or anti-beta2-glycoprotein I antibodies present in plasma, on two or more occasions at least 12 weeks apart. ALthough the presence of LAC correlates best with thrombosis, the Laboratory testing of LAC is not well standardized. In this article, the Laboratory evaluation of LAC will be explained, including the different tests that are recommended by the Israeli Sub-committee of Thrombosis and Hemostasis Laboratories, the possibility to evaluate LAC in patients treated with antithrombotic therapy, and how to report and interpret the results.

Protein Z levels and central retinal vein or artery occlusion.

OBJECTIVES: Central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) are common disorders associated with risk factors for atherosclerosis. Protein Z is a cofactor for the inactivation of activated factor X (Xa) by the protein Z dependent protease inhibitor. Protein Z deficiency was recently linked to increased risk of arterial thrombosis. We investigated whether CRVO and CRAO are associated with low protein Z levels. PATIENTS AND METHODS: Patients with CRVO, CRAO or recurrent branch retinal vein occlusion were recruited to the study. Protein Z level, lupus anticoagulant (LAC), anticardiolipin antibodies (ACA) and activated protein C resistance (APCR) were determined in plasma from patients (n = 36) and healthy controls (n = 42). RESULTS: Thirty patients in the study group had traditional risk factors for retinal vessel occlusion and six patients had none. There was no significant difference in protein Z levels between the whole study group patients and controls (1995 +/- 810 vs. 2010 +/- 603 ng/mL, P = 0.922). However, patients with no risk factors for retinal vessel occlusion had significantly lower protein Z levels than controls (1379 +/- 682 vs. 2010 +/- 603 ng/mL, P = 0.022). Positive LAC was found in six patients and one control subject (P = 0.04). There were three patients and one control subject with abnormal APCR (P = 0.3) and none with positive ACA. Low protein Z level (lower than fifth percentile of control) was not associated with the presence of LAC or APCR. CONCLUSION: Low protein Z level may be another risk factor for retinal vessel occlusion in patients without traditional risk factors for these disorders.