Document Type : Case Report Article
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
Main Subjects
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).
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 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 |
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).
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?
We want to thanks all researcher and health care providers in recent COVID-19 infection crisis.
The authors declared no conflicts of interest.