Farname Inc. in collaboration with Iranian Society of Gynecology Oncology

Authors

1 Department of Obstetrics and Gynecology, Faculty of , University of , , Iran

2 Department of Obstetrics and Gynecology, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background & Objective: Since the first reported respiratory distress syndrome due to the new version of the coronaviruses family, COVID-19, there is a concern about the possible maternal and perinatal outcome of new infection in a short and even long time, our information about the prognosis of pregnancy in sync with COVID-19 is limited. What is our task as scientists in eliminating the unknown facts?
Materials & Methods: Here we try to present a couple of pregnant cases in their third trimesters of pregnancy that complicated with two contrary complication of COVID-19 infection, intending to illuminate the best management strategy in COVID-19 infected pregnant.
Results: The first case had experienced thromboembolism, and also bleeding accident, who fortunately survived unlike the other case, who expired due to multi-organ failure and impossibility of anticoagulant agent administration for the suspected pulmonary thromboembolic accident.
Conclusion: The prior report revealed the thrombo-inflammatory and hypoxic effect of COVID-19 that could lead to microvascular thrombosis and progression, which enforce health care providers, introducing the anticoagulant agents to decline COVID-19 mortality, especially in a critically ill patient. Pregnancy is associated with coagulation abnormality which could intensify the COVID-19-induced coagulopathy. But, one should balance the harm and benefit of such a hazard approach, is there any concern about vascular damage of COVID-19 and subsequent bleeding, that could be exacerbated with high dose anticoagulant agent administration? The other question that we want to discuss in the present report is about comparing the cost and benefit of anticoagulant therapy?

Keywords

Introduction


Since the world organization announcement for an emergent situation due to the novel Coronavirus pandemic, this virus has shown aggressive nature, different manifestations, and a high fatality rate. Venous thromboembolism (VTE) be considered as one of the profound features in this regard, as there is a strong suggestion on the need for thrombo-prophylaxis in confirmed cases (1-3). As there is no relevant evi-dence on the susceptibility of pregnant cases with under-ling physiologic changes for this viral infection in comparison with prior coronaviruses epidemics, (4-6) and above that the least hazard management in this population, in the present study we aim to discuss this challenging issue, by introducing a pair of pregnant cases with the discrete outcome and reviewing others advice (7).

 

Materials and Methods

A couple of pregnant-cases have been selected from the hospitalized patient in a level 3 maternity hospital in Iran, with a certain diagnosis of COVID-19 based on reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and oropharyngeal speci-men and presence of ground-glass-opacities in the chest-CT scan. The ethical committees' rules are consi-dered in this report. The patient signed the informed consent in the aim of reporting the present article.


 

Finding

There were 2 admitted pregnant-cases (gravida 2, para1) with a similar presentation, fever, myalgia, respiratory discomfort, and tachycardia (between 120-140beat/min) but normal peripheral oxygen saturation (O2Sat). Although the administration of broad-spec-trum antibiotics, prophylactic anti-coagulant, hydroxyl-chloroquine, and Atazanavir was considered, the prog-nosis was not favorable; both cases experienced mate-rnal morbidity or mortality.

Case 1

A 32-year-old gravida woman at 34/3 weeks of gestation (GW) with a history of diet-controlled gestational diabetes, hypothyroidism, and recent con-tact with multiple cases of confirmed COVID-19 was admitted with a typical presentation. Deteriorating symptoms in subsequent days (Table 1), lead to a diagnosis of pulmonary thromboembolic accident (PTE) based on an MDCT scan (Figure 1), so anticoagulant-agent was prescribed in therapeutic dose. Despite, a dramatic response in respiratory status, a sudden sever vaginal-bleeding accident, because of placental abruption, ended up to emergent caesarian delivery. Now, after 6 weeks of termination, both patient and her-male fetus are in complete remission.

Case 2

A 21-year-old gravida woman at 21 GW had been referred with a similar presentation. But due to deteriorating symptoms within 48 hours with no response to vasopressors agent, intubation was planned for her (Table 2, Figure 2). Despite all efforts, unjustified uterine contractions ended up in spontaneous delivery of a nonviable male neonate, what lately considered because of placental thrombosis. Although patient-health status, had initially shown an affirmative response to daily-plasmapheresis, on HD28, her condition regressed again and PTE was suggested based on elevated Pulmonary arterial pressure (in about 45-50) and heart failure (EF near15%). Unfortunately, there was no permission for anticoagulant therapy initiation because of thrombocytopenia and coagulopathy and she died over the next two days by worsening of cardiopulmonary status.

 
 Figure 1. Chest HRCT of the patient during hospitalization: bilateral peripheral grand glass opacity
Figure 1. Chest HRCT of the patient during hospitalization: bilateral peripheral grand glass opacity

Figure 2. Chest HRCT of the patient during hospitalization: bilateral peripheral grand glass opacity 
Figure 2. Chest HRCT of the patient during hospitalization: bilateral peripheral grand glass opacity

 
Table 1. Laboratory Data of second patient during hospitalization

  Firth day of admission Second day of admission Third day of admission Eight day of admission Last day of admission
Leukocytes × 10 /L 7000 7200 13100 5100 15400
Lymphocytes, % 20 13.7 8.4 27 18
Neutrophils, % 75 84.3 90 63 78
Platelets × 109/micL 155000 173000 200000 239000 251000
Hemoglobin, gr/dL 12.7 13 12.9 11.8 10.1
ESR, mm/h 29 NA NA NA NA
CRP, mg/L 39 45 NA NA NA
Creatinine, mg/dL 0.9 0.9 0.9 0.8 0.7
BUN mg/dL 7 10 10 8 6
Na, mEq/L 137 138 137 142 141
Ka, mEq/L 4.5 4.7 4.5 3.5 3.9
Protein (U/A) neg NA NA NA NA
Blood (U/A) neg NA NA NA NA
WBCs, hpf (U/A) neg NA NA NA NA
RBCs, hpf (U/A) neg NA NA NA NA
Pr/Cr(U/A) 0.1 NA NA NA NA
Albumin, g/L 3.5 3.5 NA NA NA
AST, U/L 24 25 NA NA NA
ALT, U/L 10 8 NA NA NA
Bilirubin 0.4 0.6 NA NA NA
LDH, U/L 518 590 NA NA NA
D-Dimer(µg/mL) 3.1 2.6 1.9 1.6 1.3
FDP 24 24 NA NA NA
CPK U/L 71 NA NA NA NA
PT, seconds 11.4 11 11 NA 27.5
PTT, seconds 47 50 56 50 55
INR 1 1 1 NA 2.5
Fibrinogen 300 302 NA NA NA
Cardiac troponins 0.2 NA NA NA NA
Ferritin 81 NA NA NA NA
Procalcitonin (µg/L) 0.4 NA NA NA NA
TSH 0.75 NA NA NA NA

 

Table 2. Laboratory Data of second patient during hospitalization

  First day of hospitalization First day of ICU admission Second day of ICU admission The day after 7 session of plasma exchange Third weeks of hospitalization Fourth weeks of hospitalization Last day of hospitalization
Leukocytes × 10 /L 4300 3900 10500 13200 15100 8200 5000
Lymphocytes, % 25 20 17 22 3.4 4.7 11
Neutrophils, % 71 77 80 73 94 92 84
Platelets × 109/micL 71000 59000 33000 56000 70000 41000 36000
Hemoglobin, gr/dL 10.6 10.7 8.4 7.9 11 7.8 7.3
ESR, mm/h 23 NA NA NA NA NA NA
CRP, mg/L 55 58 51 27 71 110  
Creatinine, mg/dL 0.8 1 2.5 3.4 4.4 3 2.4
BUN mg/dL 7 9 23 63 78 73 60
Na, mEq/L 131 145 150 148 135 131 136
Ka, mEq/L 3 4.7 4.6 4 4.6 4.3 4.2
Protein (U/A) 1+ NA NA NA NA NA NA
Blood (U/A) trace NA NA NA NA NA NA
WBCs, hpf (U/A) 1-2 NA NA NA NA NA NA
RBCs, hpf (U/A) Neg NA NA NA NA NA NA
Pr/Cr(U/A) 0.9 NA NA NA NA NA NA
Albumin, g/L 3.4 NA NA NA NA NA NA
AST (U/L) 107 500 3126 110 30 26 30
ALT (U/L) 96 216 1500 44 13 20 25
Bilirubin 2.9 NA 6.9 3.8 3.3 3.4 2.4
LDH (U/L) 746 4051 4061 1457 1096 823 705
D-Dimer (µg/ml) >10 NA >10 6.3 >5 2.5 3.3
FDP 45 NA NA NA 45 39 NA
CPK U/L 123 NA NA NA NA NA NA
PT, seconds 16 19.5 21 11.9 12.3 NA 13
PTT, seconds 48 68 65 36 39 34 35
INR 1.48 1.77 2 1.08 1.17 NA 1.1
Fibrinogen 237 242 201 285 211 242 246
Cardiac troponins <0.02 NA NA NA NA NA NA
Ferritin NA 739 >1650 NA NA NA NA
procalcitonin(µg/l) NA >10 NA 0.5 7.5 NA NA
APS test NA normal NA NA NA NA NA


 

Discussion

The restricted data on the COVID-19 in pregnancy and its exact management warranted more attempt to study this virus's mechanism of action. Above, the suggested association of COVID-19 with inflammatory cytokine crisis, endothelial damage, and overexpression of tissue factor, it sounds the COVID-19-induced hypoxia could cause marked blood viscosity and hyper coagulative state (7-9). Although the effectiveness of elevated D-dimer in the prediction of thrombo-inflammatory complication of COVID-19 is suggested in the present report, its pregnancy accuracy is on the debate (8). Taking into account the progressive course of illness in present cases with elevated D-dimer, there is an obvious need for more study on the potential usage of D-dimer in the hospitalization of COVID-19 patients. The other concern about COVID-19 and pregnancy is the duplicated chance of VTE, so, is it reasonable to prescribe higher-dose of the anticoagulant agent in this population? There is a contrary feature by this virus, thrombin generative tendency as described before, and on the other hand bleeding potential due to dysfunction of the angiotensin-converting enzyme (ACE) 2 receptor and endothelial cell damage, (10, 11) Considering the potential side-effect of anticoagulant and besides, the parallel complication in COVID-19 makes this sugges-tion more complex. Moreover, one should justify the risk of perinatal morbidity in comparison with maternal out-come (5, 9). Hypoxic effect of COVID-19 on the placenta and risk of thrombosis and abruption, and also inflammatory-induced endothelial cell damage and bleeding threat should be mentioned at the time of anti-coagulants administration (12-14).
 

 
Conclusion

Although there is minimal supporting data, the need for prescribing the risk-based-adjusted dose of an anti-coagulant agent in the aim of eliminating the bleeding potential sounds essential. But, according to the docu-mented benefit of anticoagulant prescription in COV-ID-19 cases with positive predictive factor, and the bleeding tendency of either COVID-19-induced circu-mstance or the anticoagulant agent, is there an under-estimated need for hospitalization and monitoring of high-risk pregnant population during their treatment?

 

Acknowledgments

We want to thanks all researcher and health care providers in recent COVID-19 infection crisis.

 

Conflicts of Interest

The authors declared no conflicts of interest.
 

 
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