CLINICAL PROTOCOL FOR DIAGNOSIS AND TREATMENT OF IMMUNE THROMBOCYTOPENIA DURING PREGNANCY

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CLINICAL PROTOCOL FOR DIAGNOSIS AND TREATMENT OF IMMUNE

THROMBOCYTOPENIA DURING PREGNANCY

Makhmonov Lutfullo Saydullayevich

Chief Physician, Samarkand Regional Multidisciplinary Medical Center;

Head of Hematology Department, Samarkand State Medical University

Abbosova Sanobar Aslanovna

Gynecologist, Gynecology Department,

Samarkand Regional Multidisciplinary Medical Center

Umarov Zafar Mardonovich

Head of Gynecology Department,

Samarkand Regional Multidisciplinary Medical Center

Uzakova Oyjamol Narzullaevna

Assistant, Hematology Department,

Samarkand State Medical University

Abstract.

Immune thrombocytopenia (ITP) during pregnancy presents significant diagnostic

and therapeutic challenges due to the potential risks to both mother and fetus. This study

aimed to develop and validate a clinical protocol for the diagnosis and management of ITP

in pregnant patients. A total of 62 pregnant women with confirmed ITP were treated

according to a stepwise protocol involving initial corticosteroid therapy, intravenous

immunoglobulin (IVIG) for corticosteroid-resistant or contraindicated cases, and second-line

agents for refractory patients. Diagnostic workup excluded other causes of

thrombocytopenia, ensuring accurate diagnosis. The protocol demonstrated high efficacy

with favorable maternal and neonatal outcomes, including minimal bleeding complications

and safe delivery conditions. Corticosteroids and IVIG were generally well tolerated, though

careful monitoring for adverse effects was necessary. This protocol provides a practical,

evidence-based framework for managing ITP during pregnancy, improving treatment

outcomes and patient safety. Further studies are recommended to optimize therapy and long-

term follow-up.

Keywords:

Immune thrombocytopenia, pregnancy, clinical protocol, corticosteroids,

intravenous immunoglobulin, diagnosis, treatment, maternal outcomes, neonatal outcomes,

refractory ITP

Introduction

Immune thrombocytopenia (ITP) during pregnancy represents a significant clinical

challenge due to its potential adverse effects on both maternal and fetal health. ITP is an

autoimmune disorder characterized by isolated thrombocytopenia, defined as a platelet count

below 100 × 10^9/L, resulting from increased platelet destruction and impaired platelet

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production caused by autoantibodies directed against platelet antigens. In pregnancy, the

diagnosis and management of ITP require careful differentiation from other causes of

thrombocytopenia, such as gestational thrombocytopenia, preeclampsia, HELLP syndrome,

and other hematologic or systemic disorders. The physiological changes of pregnancy,

including hemodilution and increased platelet turnover, further complicate diagnosis and

treatment decisions.

The clinical importance of immune thrombocytopenia during pregnancy lies in the risk it

poses to both the mother and fetus. For the mother, severe thrombocytopenia increases the

risk of bleeding complications during pregnancy, labor, and delivery, which can lead to

maternal morbidity and mortality if not managed appropriately. For the fetus and neonate,

there is a risk of thrombocytopenia secondary to transplacental passage of maternal

antiplatelet antibodies, which may result in bleeding complications such as intracranial

hemorrhage. Hence, the primary goal of management in pregnant patients with ITP is to

maintain a safe platelet count that minimizes bleeding risk while avoiding unnecessary

interventions that may endanger the fetus.

Currently, clinical protocols for diagnosing and treating ITP during pregnancy vary widely,

reflecting a lack of universally accepted guidelines. The diagnostic approach typically

begins with thorough clinical evaluation, exclusion of other causes of thrombocytopenia,

and laboratory investigations, including platelet counts, peripheral blood smear examination,

and tests for autoimmune markers. Bone marrow examination is rarely required unless other

hematologic conditions are suspected. Treatment strategies must be individualized based on

the severity of thrombocytopenia, bleeding risk, gestational age, and response to therapy.

First-line treatment usually involves corticosteroids or intravenous immunoglobulin (IVIG),

both of which are considered relatively safe during pregnancy. Corticosteroids act by

suppressing the immune response and reducing platelet destruction, while IVIG interferes

with Fc receptor-mediated platelet clearance. However, long-term corticosteroid use is

associated with maternal complications such as gestational diabetes, hypertension, and

increased risk of infections. IVIG, while effective, is costly and may require repeated

administrations. Other second-line therapies, such as rituximab, thrombopoietin receptor

agonists, and splenectomy, have limited data regarding safety in pregnancy and are generally

reserved for refractory cases.

The development of a clinical protocol that standardizes the diagnosis and management of

immune thrombocytopenia in pregnancy is crucial to optimize maternal and fetal outcomes.

Such a protocol should include clear diagnostic criteria, risk stratification, treatment

algorithms, and recommendations for monitoring during pregnancy, delivery, and the

postpartum period. Furthermore, interdisciplinary collaboration among obstetricians,

hematologists, and neonatologists is essential to provide comprehensive care.

In addition to clinical management, counseling patients about the disease, its potential

complications, and treatment options is vital to ensure informed decision-making and

adherence to therapy. Monitoring should also extend beyond delivery, as postpartum flare-

ups of thrombocytopenia can occur, necessitating ongoing evaluation and treatment

adjustments.

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Given the variability in presentation and response to treatment, as well as the risks

associated with both disease and therapy, evidence-based clinical protocols can assist

healthcare providers in balancing the benefits and risks of intervention, reducing morbidity,

and improving quality of life for pregnant women with ITP. This article aims to review the

current understanding of the pathophysiology, diagnosis, and treatment options for immune

thrombocytopenia in pregnancy and to propose a practical clinical protocol for its

management.

Methods

This study was conducted as a prospective observational analysis combined with a protocol

development phase at the Department of Obstetrics and Hematology in a tertiary care

hospital specializing in maternal-fetal medicine. The study period spanned two years, from

January 2022 to December 2023. The aim was to develop and validate a clinical protocol for

the diagnosis and management of immune thrombocytopenia (ITP) in pregnant women.

Pregnant women diagnosed with thrombocytopenia (platelet count < 100 × 10^9/L) who

were referred to the hematology and obstetrics departments were enrolled consecutively.

Inclusion criteria were: confirmed pregnancy at any gestational age, platelet count below

100 × 10^9/L on at least two separate tests spaced one week apart, and no other known

causes of thrombocytopenia at presentation. Exclusion criteria included: patients with pre-

existing hematologic malignancies, systemic lupus erythematosus (SLE) or other

autoimmune diseases, preeclampsia, HELLP syndrome, or other medical conditions known

to affect platelet counts.

All participants underwent a comprehensive diagnostic evaluation to differentiate ITP from

other causes of thrombocytopenia during pregnancy. Initial laboratory investigations

included complete blood count with peripheral smear, reticulocyte count, liver and renal

function tests, coagulation profile, and tests for viral infections such as HIV, hepatitis B and

C. Antinuclear antidiv (ANA) testing and direct antiglobulin test (Coombs test) were

performed to exclude autoimmune hemolytic anemia or systemic autoimmune diseases.

Bone marrow aspiration was reserved for cases with atypical features, such as abnormal

peripheral smear morphology, leukopenia or anemia, or lack of response to standard therapy.

Gestational age was confirmed by ultrasonography, and fetal well-being was monitored

throughout pregnancy.

Patients were assessed clinically for bleeding manifestations, including petechiae,

ecchymosis, mucosal bleeding, and any major hemorrhagic events. Bleeding severity was

graded using a standardized bleeding score system. Platelet counts and clinical status were

monitored every 1-2 weeks, with more frequent assessments for patients with platelet counts

below 30 × 10^9/L or active bleeding.

The clinical protocol was developed based on existing international guidelines (American

Society of Hematology, British Society for Haematology), available literature, and expert

consensus. Treatment initiation criteria were platelet counts below 30 × 10^9/L or presence

of bleeding symptoms irrespective of platelet count. First-line therapy included

corticosteroids (prednisone 0.5–1 mg/kg/day) with dose adjustments based on response and

side effects.

For patients with inadequate response or corticosteroid contraindications, intravenous

immunoglobulin (IVIG) at 1 g/kg daily for two consecutive days was administered. In

refractory cases, second-line therapies including rituximab or thrombopoietin receptor

agonists were considered, with multidisciplinary team approval.

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Delivery planning involved coordinated efforts between hematologists and obstetricians to

maintain platelet counts above 50 × 10^9/L for vaginal delivery and 80 × 10^9/L for

cesarean section. Neonates were monitored for thrombocytopenia post-delivery.

Data on demographics, clinical presentation, laboratory values, treatment regimens, and

outcomes were systematically recorded in a secured database. Treatment response was

defined as an increase in platelet count above 50 × 10^9/L and absence of bleeding. Safety

was assessed by monitoring maternal side effects and fetal complications.

Statistical analysis was performed using SPSS version 25.0 (IBM Corp., Armonk, NY).

Descriptive statistics summarized patient characteristics and outcomes. Comparisons

between treatment groups were made using chi-square tests for categorical variables and t-

tests or Mann-Whitney U tests for continuous variables. A p-value of <0.05 was considered

statistically significant.

Results

During the study period, 75 pregnant women with thrombocytopenia were initially screened,

and after applying exclusion criteria, 62 patients met the inclusion criteria and were enrolled.

The mean age of participants was 29.4 ± 5.8 years, with a gestational age at diagnosis

averaging 16.2 ± 6.3 weeks. Baseline platelet counts ranged from 8 × 10^9/L to 95 × 10^9/L,

with a median of 38 × 10^9/L. All patients underwent thorough diagnostic evaluation to

exclude other causes of thrombocytopenia. Peripheral blood smear analysis showed isolated

thrombocytopenia without abnormal platelet morphology in 58 patients. Four patients with

atypical features underwent bone marrow aspiration, which ruled out malignancies and other

hematologic disorders. Viral serologies were negative, and autoimmune markers were

positive in six patients without fulfilling systemic lupus erythematosus criteria. Gestational

thrombocytopenia was excluded based on platelet counts and clinical findings, confirming

immune thrombocytopenia diagnosis in all participants.

Clinically, 64.5% (40 patients) presented with bleeding symptoms at diagnosis, mostly mild

mucocutaneous bleeding such as petechiae and ecchymoses, with five patients experiencing

moderate mucosal bleeding including epistaxis and gingival bleeding. No major

hemorrhagic events were observed at baseline. All patients received treatment according to

the developed clinical protocol. Corticosteroids were administered as first-line therapy in 48

patients (77.4%), while 14 patients (22.6%) received intravenous immunoglobulin (IVIG)

due to corticosteroid contraindications or resistance. In the corticosteroid group, 79.2%

achieved complete response, defined as platelet counts above 50 × 10^9/L within four weeks,

with a median response time of 18 days. Eight patients showed partial response, and two

were non-responders. Among patients receiving IVIG, 85.7% achieved complete response

with a faster median response time of seven days. Two patients required second-line

therapies.

Refractory cases totaled six, with four patients treated successfully with rituximab,

achieving platelet stabilization above 50 × 10^9/L within six weeks, while two patients

responded to thrombopoietin receptor agonists. Maternal bleeding complications during

pregnancy and delivery were minimal, with platelet counts maintained above the threshold

levels necessary for safe vaginal delivery (50 × 10^9/L) and cesarean section (80 × 10^9/L).

Neonatal outcomes were favorable, with no cases of severe thrombocytopenia or intracranial

hemorrhage reported. Mild transient neonatal thrombocytopenia was noted in five newborns,

resolving spontaneously within two weeks postpartum.

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Regarding safety, corticosteroid therapy was associated with gestational diabetes in five

patients and hypertension in three, while IVIG was generally well tolerated with only mild

infusion reactions in three cases. No serious adverse events occurred. Overall, the clinical

protocol proved feasible and safe in clinical practice, yielding high treatment response rates

and low rates of complications, confirming its applicability for managing immune

thrombocytopenia during pregnancy.

Discussion

Immune thrombocytopenia (ITP) during pregnancy remains a complex condition requiring

careful diagnostic evaluation and individualized treatment approaches to minimize risks to

both the mother and fetus. The results of this study demonstrate that a structured clinical

protocol incorporating established diagnostic criteria and a stepwise treatment algorithm can

effectively guide clinicians in managing ITP in pregnant patients, ensuring favorable

outcomes and minimizing complications.

The diagnostic process outlined in the protocol successfully distinguished ITP from other

causes of thrombocytopenia, such as gestational thrombocytopenia and secondary

autoimmune or hematologic conditions. This differentiation is critical, as the management

and prognosis vary significantly between these conditions. In particular, the use of thorough

clinical assessment combined with targeted laboratory testing, including peripheral smear,

autoimmune markers, and selective bone marrow examination, allowed for accurate

diagnosis in the majority of cases. This approach aligns with recommendations from

international hematology societies, emphasizing the need for exclusion of secondary causes

before confirming ITP.

Our findings corroborate previous reports indicating that corticosteroids remain the

cornerstone of first-line therapy in pregnant women with ITP. The high response rate

observed with corticosteroids in this study (79.2%) supports their efficacy in increasing

platelet counts while providing a relatively safe profile when used judiciously during

pregnancy. However, the associated maternal side effects, including gestational diabetes and

hypertension, underscore the importance of careful monitoring and dose adjustment to

mitigate these risks. The protocol’s inclusion of IVIG as an alternative or adjunctive therapy

provided an effective option for patients who were steroid-resistant or had contraindications,

with a faster median time to platelet recovery noted in the IVIG group. This finding is

consistent with the literature that supports IVIG’s role in rapid platelet count elevation,

especially in cases where urgent intervention is required.

Refractory cases posed a significant clinical challenge, and the protocol’s recommendation

to consider second-line agents such as rituximab and thrombopoietin receptor agonists

proved beneficial. Although data on the safety of these agents in pregnancy remain limited,

their use in selected cases under multidisciplinary supervision facilitated platelet

stabilization and reduced bleeding risk. These findings highlight the need for ongoing

research into novel therapeutic options and their safety profiles in pregnant patients with

refractory ITP.

The favorable maternal and neonatal outcomes observed in this study are particularly

noteworthy. Maintaining platelet counts above critical thresholds during delivery is essential

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to minimize hemorrhagic complications. The protocol’s coordinated care approach between

hematologists and obstetricians ensured appropriate timing and preparation for delivery,

with no major maternal bleeding events reported. Neonatal monitoring identified a small

proportion of infants with transient thrombocytopenia, which resolved without intervention,

reflecting the known risk of passive antidiv transfer. This emphasizes the importance of

neonatal platelet surveillance and readiness to manage potential complications.

The safety profile of the treatments used within the protocol supports their continued use in

pregnancy, albeit with vigilance for adverse effects. The balance between treatment benefits

and potential risks requires individualized decision-making, taking into account disease

severity, gestational age, and patient preferences. Furthermore, the protocol facilitates

patient counseling and education, empowering women to participate actively in their care,

which can improve adherence and outcomes.

Conclusion

In conclusion, the clinical protocol developed and validated through this study offers a

practical and evidence-based framework for diagnosing and managing immune

thrombocytopenia in pregnancy. It enables effective treatment initiation, appropriate

monitoring, and timely escalation of therapy while minimizing risks to both mother and

child. Future multicenter studies with larger cohorts are needed to refine these

recommendations further and explore long-term maternal and neonatal outcomes. Continued

collaboration among hematologists, obstetricians, and pediatricians will remain essential to

optimize care for this vulnerable population.

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