Successful vaginal delivery in very severe malarial thrombocytopenia: a case report

Abstract

Background

Very severe thrombocytopenia, characterized by a platelet count below 20,000/µL, in pregnant women with malaria, particularly Plasmodium falciparum infection, is a significant concern due to its association with increased mortality. While not always associated with bleeding, it can be a sign of severe disease and may require prompt intervention.

Case presentation

The author presents a rare case of a successful vaginal delivery in a 22-year-old, Para II, woman from Western Ethiopia, who had very severe malarial thrombocytopenia. She started treatment with artesunate for acute malaria at the local health center, which subsequently referred her to a tertiary hospital for more comprehensive care. At this hospital, she completed a course of artesunate and received a transfusion of packed blood cells. Labor commenced spontaneously, and she delivered a live newborn without any postpartum hemorrhage. During the postpartum period, she was monitored and subsequently discharged with a significant improvement in platelet counts.

Conclusion

Malarial thrombocytopenia is one of the significant complications associated with malaria during pregnancy. It typically presents as asymptomatic, even when platelet counts are very low. In contrast to thrombocytopenia caused by other factors, early diagnosis and prompt treatment with antimalarial medications can lead to improved outcomes for both the mother and the fetus.

Introduction

Malaria arguably has influenced more of human history than any other disease. It continues to pose a serious risk to public health, especially in settings with limited resources. Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale are among the species that cause it. The majority of deaths from malaria are caused by Plasmodium falciparum [1–3].

Pregnant women are more susceptible to malaria than their non-pregnant counterparts [4–6]. This is due to suppression of cell-mediated immunity and preferential sequestration of parasites in the placenta [6]. Malaria during pregnancy is associated with poor maternal and fetal outcomes [5, 6] including maternal anemia, maternal thrombocytopenia, abortion, intrauterine fetal death (IUFD), intrauterine growth restriction (IUGR), preterm delivery, and low birth weight [5, 6]. The case fatality rate of malaria in pregnancy can be as high as 50% [6].

Efforts to combat malaria have included the development of vaccines, intermittent preventive therapy (IPT), improved diagnostic tools, and the distribution of insecticide-treated bed nets. Despite these advancements, the disease continues to persist, underscoring the need for ongoing research and investment in prevention and treatment strategies [2, 6, 7].

Anemia and thrombocytopenia are the two most common hematologic complications of malaria in pregnancy. In most cases, thrombocytopenia is not associated with bleeding and requires no treatment, with the platelet count rapidly returning to normal after successful treatment of the malarial episode [6, 8]. Here, the author presents a case of successful vaginal delivery in a pregnant woman complicated with very severe malarial thrombocytopenia.

Case presentation

A 22-year-old Western Ethiopian woman, who is para II, came to a tertiary hospital. She claims to have been amenorrheic for the past nine months, but she cannot remember when she had her last normal menstrual period (LNMP). She began taking artesunate when the local health center diagnosed her with severe malaria. At presentation; she had tinnitus, vertigo, headache, fever, shortness of breath, and easy fatigability. She had been treated for malaria a month back. She has no abnormal body movement, vaginal bleeding, blurring of vision, or epistaxis. She has no pushing down pain or passage of liquor.

She had three antenatal care (ANC) contacts during the current pregnancy, during which she received iron and folic acid supplements. In addition, she received two doses of tetanus toxoid. No other interventions, including malaria prophylaxis, were given to the patient. Her prior medical records are unremarkable. She has never had heart disease, hypertension, diabetes, or bronchial asthma. Her past surgical, personal, and social histories are not significant. She denied family history of hematological diseases.

The patient was acutely sick. Her vital signs were: blood pressure 100/70 mmHg, pulse rate 116 beats per minute, respiratory rate 24 breaths per minute, and temperature 36.5 °C. She presented with pale conjunctivae. The lymphatic, chest, and cardiovascular systems were normal. Abdominal examination showed a 34-week-sized uterus in a longitudinal lie with a cephalic presentation, no uterine contractions, and a fetal heartbeat of 144 beats per minute. The genitourinary system showed no costovertebral angle tenderness. She had palmar pallor and was oriented to time, person, and place. Reflexes were normal, with no neurologic deficits. Blood group, random blood sugars (RBS), peripheral morphology, stool examination, coagulation profile, thyroid function test, VDRL, HBsAg, renal function test, liver function test (Table 1), and serial complete blood count (CBC) (Table 2) were done.

Table 1.

Laboratory investigations of pregnant woman diagnosed with acute malaria and treated at a tertiary hospital in Western Ethiopia, 2024

Laboratory tests	Results	Normal range
Blood film*	Plasmodium Falciparum
Urinalysis	Non-revealing
Stool exam	No ova or parasite seen
RBS	108mg/dl
Blood group	B +
PT	12.05 seconds	11–13.5 seconds
INR	0.98	1
T4	100.1 mmol/l	86–181 mm/l
TSH	3.77 mIU/L	0.3–4.2 mIU/L
Peripheral morphology	✓No blast cells ✓Normocytic hypochromic RBCs
ALT	22.4 U/L	0–33 U/L
AST	28 U/L	0–32 U/L
Creatinine	0.62 mg/dl	0.5–0.9 mg/dl

ALT, alanine transaminase; AST, aspartate aminotransferase; INR, International Normalized Ratio; PT, prothrombin time; RBC, red blood cell; RBS, random blood sugar; TSH, thyroid stimulating hormone; T4, thyroxin; done at health center*

Table 2.

Platelet counts, hemoglobin, and WBC counts of pregnant woman diagnosed with acute malaria and treated at a tertiary hospital in Western Ethiopia, 2024

Date	Platelet count	Hemoglobin	WBC	Remark
22/12/24	10,000 cells/μL	5.1 g/dl	6500 cells/μL	1st dose of artesunate**
23/12/24	9000 cells/μlL	2.6 g/dl	11,500 cells/μL	** transfused twice
24/12/24	6000 cells/μ	6.1 g/dl	5600 cells/μL	In the morning**
24/12/24*	3000 cells/μL	5.6 g/dl	7000 cells/μL	In the evening**
25/12/24	7000 cells/μL	7.3 g/dl	4600 cells/μL	**
26/12/2024	5000 cells/μL	7.3 g/dl	4750 cells/μL	**
27/12/204	6000 cells/μL	8.5 g/dl	3700 cells/μL
29/12/24	6000 cells/μL	7.6 g/dl	5760 cells/μL
30/12/2024	24,000 cells/μL	7 g/dl	12,300 cells/μL	Last dose of artesunate **
02/1/25	34,000 cells/μL	7.9 g/dl	4500 cells/μL
17/1/25	74,000 cells/μL	9 g/dl	5900 cells/μL
05/2/25	105,000 cells/μL	9.6 g/dl	6500 cells/μL

WBC, white blood cell; date of delivery*; transfusion with packed blood**

Obstetrics ultrasound examination showed aggregate gestational age of 33 weeks, estimated fetal weight (EFW) = 2119 g, longitudinal lie, cephalic presentation, reassuring biophysical profile, fundal placenta, and adequate amniotic fluid.

With the final diagnosis of very severe thrombocytopenia, acute malaria, and third-trimester pregnancy, the patient was admitted. The antimalarial agent was continued. For lung maturation, she was given intramuscular dexamethasone 6mg twice a day for 2 days. After transfusing her with three units of whole blood, the plan was to refer her to a better setting where she could get fresh frozen plasma and platelets. Unfortunately, she developed pushing down pain and rupture of membranes. On digital examination, the cervix was 5 cm dilated, vertex presentation, and the membranes were ruptured. She was then followed for the progress of labor. She gave birth to a male alive neonate weighing 2200 g with Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) scores of 8 and 9 at 1st and 5th minute, respectively. There was no episiotomy or tear. She was provided with intramuscular oxytocin and tranexamic acid. During the postpartum period, she was monitored and subsequently discharged with a significant improvement in platelet counts.

In accordance with the discharge instructions and follow-up plan, the patient returned to the hospital at six and twelve weeks postpartum. Subsequent evaluations verified that the woman was recovering effectively both physically and emotionally, while the infant was achieving all developmental milestones. The laboratory tests showed that the complete blood count (CBC) profile to be within normal ranges.

Discussion

In pregnancy, thrombocytopenia is defined as a platelet count of < 150,000/μL. It complicates 7–12% of all pregnancies [7, 9, 10]. Thrombocytopenia in pregnancy is classified into mild (100,000–149,000/μL) moderate (50,000–99,000/μl), and severe (< 50,000/μL) [5, 9, 11]. It is considered very severe when the platelet counts are less than 20,000 (12). The current case presented with critical thrombocytopenia, exhibiting a platelet count as low as 3000/μL, which is among the lowest recorded levels in documented malaria case reports [12, 13].

Pregnancy-related thrombocytopenia can be either pathologic or physiological. Hemodilution, increased platelet activation and clearance cause physiologic thrombocytopenia, which is often mild to moderate [7, 14]. Numerous diseases, some of which may be specific to pregnancy or occur in other situations, are the cause of pathologic thrombocytopenia. The growing fetus and the mother may be greatly at risk from the pathological ones [7, 10]. In Ethiopia, malaria is one of the common causes of thrombocytopenia in pregnancy [11]. In this case, the patient presented with acute malaria complicated with very severe thrombocytopenia and anemia.

Numerous researches have proposed potential patho-immunological explanations of thrombocytopenia in malaria, despite the fact that the exact mechanism is still unknown [6, 12]. Thrombocyte damage or excessive platelet removal may be caused by oxidative stress, bone marrow alteration, macrophage colony-stimulating factor, immunoglobulin G binding to platelet-bound malaria antigens, spleen pooling, elevated plasma cell-free circulating nucleic acid levels in P. vivax, and platelet phagocytosis [5, 6, 11, 12].

In malaria, thrombocytopenia was usually asymptomatic. When an acute malarial infection occurs, very few pregnant women with thrombocytopenia exhibit spontaneous bleeding. There is no significant correlation between platelet counts and any bleeding [6, 12, 14]. However, when the platelet count drops below 10,000/μL, spontaneous bleeding may happen [15].

Given that malarial thrombocytopenia is typically asymptomatic, it is crucial to rule out malaria in pregnant women with low platelet counts and to conduct additional investigations for the disease, especially in regions where malaria is wide spread [6, 12]. In the current case, despite very low platelet counts, there is no bleeding from body sites, antepartum hemorrhage (APH), or post-partum hemorrhage (PPH).

There is currently no solid data on how to treat patients who have both thrombocytopenia and malaria. Although platelet transfusion has been routinely used, its effectiveness has not been shown. When platelet counts are less than 10,000/μL, the recommendation for prophylactic platelet transfusion most likely only applies in cases where the bone marrow is impaired and unable to produce effective platelets. The presence of hemorrhage, suspected disseminated intravascular coagulation (DIC), and extremely low platelet counts are some reasons for platelet transfusion. These findings highlight the scant evidence currently available supporting the recommendations for platelet transfusion in these patients [6–8]. The transfused platelets are not spared by peripheral immunological mechanisms of destruction. As a result, clinicians must carefully weigh the benefits and risks associated with platelet transfusions in such cases [8]. The multifaceted approach to antimalarial treatment reveals a notably optimistic outlook for patient recovery, particularly with respect to thrombocytopenia, which tends to resolve in the majority of cases. The median time for recovery from malaria associated thrombocytopenia is 7 (2–14) days and did not differ by treatment regimen [6, 16]. Furthermore, the prognosis remains encouraging across all species that infect humans, indicating a general resilience in affected patients. Despite the absence of robust evidence supporting immune-mediated destruction of platelets, the decision not to employ corticosteroids further underscores a strategic focus on tailored interventions that prioritize patient wellbeing. In summary, these insights underscore the importance of continued research and refined treatment protocols to enhance recovery outcomes and bolster our understanding of malaria's complex interactions within the human body. Additionally, it was discovered that dexamethasone increased the incidence of gastrointestinal bleeding and worsened neurological symptoms in patients with cerebral falciparum malaria [4, 8].

Treatment with antimalarials leads to platelet recovery. Therefore, it is important to postpone labor in women with treated uncomplicated malaria at term to allow for platelet recovery with treatment. However, this may not be the case in severe malaria, where platelet counts are severely affected [17]. The optimal management of the labor and safe delivery of fetus remains point of discussion [16]. It is advisable to boost platelet counts through transfusion for delivery when platelet count is between 10 and 50,000/μL. When an elective cesarean section is scheduled, obstetricians transfuse platelets at concentrations less than 50,000/μL [14, 15].

The risk of hemorrhage associated with normal vaginal delivery in women with severe thrombocytopenia is unknown [14, 15]. There was a reported case of PPH in one patient with a platelet count of 29,000/μL after she delivered by cesarean section despite being provided with uterotonic agents and tranexamic acid. The patient was treated with a supra-cervical hysterectomy and transfused with three units of packed cells, six units of platelets, and six units of fresh frozen plasma [6]. This suggests that her bleeding may have been effectively managed through the timely intervention and the administration of clotting factors. In the current case, despite having only 3000/μL platelets, the patient did not have PPH.

Conclusion

Malarial thrombocytopenia is one of the significant complications associated with malaria during pregnancy. It typically presents as asymptomatic, even when platelet counts are very low. In contrast to thrombocytopenia caused by other factors, early diagnosis and prompt treatment with antimalarial medications can lead to improved outcomes for both the mother and the fetus.

Abbreviations

ANC

Antenatal care

ALT

Alanine transaminase

APH

Antepartum hemorrhage

APGAR

Appearance, pulse, grimace, activity, and respiration

AST

Aspartate aminotransferase

CBC

Complete blood count

DIC

Disseminated intravascular coagulation

EFW

Estimate fetal weight

HBsAg

Hepatitis B surface antigen

IPT

Intermittent preventive therapy

IUFD

Intrauterine fetal death

INR

International normalized ratio

LNMP

Last normal menstrual period

PPH

Postpartum hemorrhage

PT

Prothrombin time

RBC

Red blood cell

RBS

Random blood sugar

TSH

Thyroid stimulating hormone

T4

Thyroxin

VDRL

Venereal disease research laboratory

Author contributions

TT wrote the manuscript and prepared the tables.

Funding

No funding is received for this study.

Data availability

The datasets used in this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

Ethical approval was obtained from the Research Ethics Review Committee of Wollega University Institute of Health.

Consent for publication

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

There are no competing interests.