Pregnancy initiates various physiological changes in the maternal body to support fetal growth. These modifications encompass alterations in maternal blood composition and the circulatory system. Specifically, pregnancy results in increased levels of clotting factors, estrogen, and progestin. These modifications or alterations contribute to a heightened susceptibility to blood clot formation and deep venous thrombosis (DVT) during pregnancy. While blood clotting is a normal defensive mechanism against excessive bleeding, it poses a substantial health danger to pregnant women (PW) and their growing fetus. Research has demonstrated an increased susceptibility among PW to develop blood clots in their lower extremities and pelvic region. Pregnancy-related blood clotting can manifest through symptoms such as leg swelling (edema), discomfort, exacerbated pain following physical activity, and the presence of swollen veins. Additionally, women with DVT or related blood clotting disorders were observed to face an increased risk of adverse health outcomes. These consequences posed potential harm to both maternal well-being and fetal development. Specifically, they were susceptible to experiencing placental blood clotting (PBC) [1, 2, 3, 4, 5].

The placenta is an important organ for food intake, gas exchange via the mother’s blood supply, waste elimination from the fetus’s blood, and fetal thermoregulation. It also fights inside infections and produces hormones that aid in pregnancy [6]. The placenta, like other organs, can suffer from medical disorders including placenta accreta, placenta previa, and PBC [1, 2]. Unfortunately, epidemiological studies suggest that PBC affects about one out of every 1,000 people in the general community [7]. Research indicates that PBC can stem from various factors, leading to serious medical complications and a heightened risk of hypercoagulability during pregnancy. This condition not only poses risks during pregnancy but also has lasting effects on both the mother and fetus due to compromised blood flow [1, 2, 3, 8]. Therefore, PW with PBC require specialized care due to an increased vulnerability to fetal loss or premature delivery. In the realm of research in this field, a proactive approach has been adopted to anticipate and tackle complications linked to PBC before they manifest symptoms. This proactive stance encompasses the systematic exploration of risk factors, advancements in diagnostic techniques, and the development of therapeutic strategies. Concurrently, efforts have been made to enhance the precision of managing PBC during pregnancy and the administration of anticoagulant therapy simultaneously [5, 7, 8].

Anticoagulants prolong coagulation, regulating clotting and reducing thrombotic tendencies. They come in various categories, including unfractionated heparin, low molecular weight heparins like clexane, and oral options like warfarin. Warfarin inhibits liver clotting factor synthesis but poses fetal risks in pregnancy, while clexane is favored for high-risk pregnancies due to its predictability and lower placental transfer risk. Adherence to anticoagulant therapy is crucial to avoid negative outcomes, as missed doses increase thrombosis risk, and excessive usage heightens bleeding risk. Lab monitoring with specific tests is necessary to assess drug effectiveness and dosage impact on coagulation in patients on anticoagulation therapy [2, 9, 10, 11].

The primary diagnostic assays for assessing coagulation irregularities consist of prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT). PT measures blood plasma clotting time, with INR obtained from PT as a standard measurement. Elevated PT, INR, and APTT indicate prolonged coagulation time and an increased risk of bleeding. Conversely, very low PT and INR levels suggest shortened coagulation time and a higher risk of blood clots. Therefore, these tests play a crucial role in monitoring coagulation status in patients with clotting or bleeding disorders, particularly in PW and those using anticoagulants such as heparin and clexane. They aid in dosage adjustment and assessing vitamin K levels for optimal patient care. PT evaluates intrinsic and common coagulation pathways, including factors I (fibrinogen), II, V, VII and X. APTT assesses intrinsic and common pathways, including kininogen, prekallikrein, and factors I, II, V, VIII, IX, X, and XII [1,2, 9, 12, 13, 14].

Blood clotting arises from interactions among vessel walls, platelets, and coagulation factors. The intrinsic pathway, initiated by endothelial damage, establishes an enduring platelet barrier strengthened by fibrin, arresting bleeding. Within this process, clotting factors VIII, IX, XII, and XI play pivotal roles. Meanwhile, the extrinsic pathway, involving factors VII and III, reacts to external injury. The convergence of these pathways forms the common pathway, engaging factors I (fibrinogen), II (prothrombin), V, X, and XIII, ensuring uninterrupted coagulation. Clotting factor IV (calcium ion), antithrombin, proteins C and S additionally modulate clot formation at bleeding sites. The balance between these elements and fibrinolysis regulates clot dynamics. In pregnancy, factors VII, VIII, X, XII, von Willebrand factor, and fibrinogen levels double compared to pre-pregnancy levels. Conversely, other clotting factors remain consistent, akin to non-pregnant levels [9, 10, 11, 12, 13].

Fibrinogen, synthesized mainly in the liver, is a plasma protein critical for blood coagulation, transforming into fibrin during coagulation. Variations in fibrinogen levels impact clotting. Elevated fibrinogen levels, often triggered by factors like inflammation and genetic or chronic inflammatory conditions such as rheumatoid arthritis, increase the susceptibility to excessive blood clot formation, leading to conditions like DVT. This association may be extend to blood clotting disorders like PBC in PW. Deficits arise from genetic or liver disorders hindering production, resulting in poor clotting or inadequate clotting [1, 2, 9, 15].

During pregnancy, changes in blood hemostasis cause oscillations in clotting factors, particularly fibrinogen and other elements, lowering natural anticoagulants and fibrinolytic activity and increasing the risk of PBC. Factors such as maternal age, stillbirth, preeclampsia, chronic ailments and obesity may further contribute to heightened PBC susceptibility during pregnancy. Critical considerations in managing PBC encompass anticoagulant choice, dosage regulation, and adherence to American Heart Association (AHA) recommended parameters for PT, INR and APTT during treatment [2, 3, 9, 16, 17, 18]. Consequently, variations in these factors among PW introduce uncertainty into the efficacy of anticoagulant therapy and associated concerns.

Notably, there has been a significant surge in PBC incidents at Jordan’s Obstetrics, Gynecology, and Pediatrics hospital in Al-Mafraq over the past five years. Moreover, no prior research in Jordan has evaluated the efficacy of anticoagulant therapy, specifically clexane, and the potential risk factors affecting its effectiveness during PBC episodes. For these reasons, this study focused on PW residing in the Al-Mafraq region of Jordan who were undergoing anticoagulant treatment for PBC. In this study, the efficacy of the anticoagulant clexane and adherence to recommended ranges for prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) by the AHA were investigated. Additionally, the impact of variable factors such as age, body mass index (BMI), blood type, and fetal sex on PT, INR, and APTT was examined. As part of the investigation, the study also aimed to evaluate plasma fibrinogen concentration (PFC) in PW with PBC who volunteered for participation.

Subjects and Study Design

This study was carried out at an Obstetrics, Gynecology, and Pediatrics hospital in Al-Mafraq, Jordan. The hospital offers free healthcare to PW and their babies, serving both Jordanian citizens and Syrian refugees. The diagnosis of PBC in PW was confirmed by an obstetrician and a hematologist. All 75 pregnant volunteers diagnosed with PBC who consented to participate in the research were exclusively recruited from the Al-Mafraq governorate. Ultimately, 40 PW with PBC met the eligibility criteria for the trial, while 35 PW with PBC were excluded for various reasons. Exclusions were made due to factors such as seeking care at a different clinic or hospital and maternal health issues requiring treatment (e.g., asthma treated with steroids, among others).

In this investigation, PW with prior PBC records received a daily subcutaneous dose of 40 mg clexane (Enoxaparin sodium, Lovenox), a prevalent low-molecular-weight heparin (LMWH) functioning as an anticoagulant. This procedure aimed to mitigate challenges arising from PBC during pregnancy. They were also instructed to take 75 mg of aspirin daily as an antiplatelet agent. These therapies were terminated at the beginning of the month preceding the projected due date of delivery. In this analysis, a group of 40 PW, all of whom were in good health and met the eligibility criteria for the research, were included as controls. The control group was chosen from the same hospital as the experimental group. There was no indication of PBC or any other blood-related illnesses or disorders in the control group.

Ethical permissions were obtained from The Higher Education Committee of Al al-Bayt University, the Ministry of Health’s ethics committee, and the associated hospital of Obstetrics, Gynecology and Pediatrics Hospital in Al-Mafraq. Each volunteer PW who agreed to participate in this study gave informed consent. All participants were also briefed on the research purpose, procedures, rights to participate, the option to discontinue without penalty, and potential risks and benefits. Following that, a signed consent form was collected from each participant PW.

Participant Characteristics and Anthropometric Measurements

Initially, PW were classified as either normal without blood clotting issues or patient with blood clotting problems. Participant data including name, age, lifestyle, medical history, and family history were meticulously documented, but no data on ethnicity or socioeconomic status were collected. All PW, both patients and controls, underwent blood group and Rh factor analysis and were subsequently categorized into eight blood type groups: O+, O-, A+, A-, B+, B-, AB+, and AB-, conforming to international standards. Lastly, the neonatal sex of all PW involved in the study was recorded post-delivery.

Anthropometric measurements, such as body weight and height, were collected by trained professionals at the hospital clinic using standardized techniques. During the initial visit, height was measured to the nearest 1 cm using a calibrated meter, with PW standing with their backs to the measuring surface, feet flat on the floor, arms at their sides, knees straight, and backs straight. Body weight was measured once at the initial visit, with a deduction of two kilograms to obtain the net body weight. Body Mass Index (BMI) was calculated as an individual’s net weight in kilograms divided by height in meters squared (\(kg/m^{2}\)). Subsequently, all participants, including both controls and patients, were classified into four subgroups based on BMI according to the World Health Organization’s (WHO) 2006 criteria: underweight (<18.5 \(kg/m^{2}\)), normal weight (18.5-24.9 \(kg/m^{2}\)), overweight (25-29.9 \(kg/m^{2}\)), and obese (>30 \(kg/m^{2}\)).

Blood Sample Collection

Under aseptic conditions, healthcare personnel obtained monthly blood samples from each patient and control during the first trimester, drawing 5 milliliters of venous blood from each PW. Blood samples were taken in tubes containing trisodium citrate anticoagulant (3.8%, 9 parts blood, 1 part anticoagulant) and each tube was labeled with the PW’s name and identifying number. The blood samples were immediately stored in an ice box and sent to the Department of Biological Sciences’ laboratory for additional processing and analysis. The blood-containing tube was centrifuged at 2500 RPM for 15 minutes at room temperature within one hour after being collected. The plasma was then pipetted into a clean plastic screw-cap vial labeled with the patient’s name and identification number.

Screening Tests for Blood Coagulation

The PT, INR, APTT, and PFC of patients and the control group were all assessed immediately. The PT test was done on plasma from blood samples obtained in trisodium citrate anticoagulant. This PT test was performed in line with the manufacturer’s procedure (withington Hospital, Manchester, United Kingdom). After repeating each sample three times, the average value was obtained.

INR can be used to detect unusual bleeding, blood clots, and to monitor patients on anti-clotting treatment. The INR stands for international normalized ratio. PW’s INR values were computed. The international sensitivity index (ISI) is utilized by the INR to equalize all thromboplastins to the reference thromboplastin using the following equation:

The APTT and PFC were measured using the manufacturer’s methodology (Diagnostica Stago; S.A.S, 92600, Asnieressur Serine, France). Each sample was run three times, and the mean of the three results was calculated.

Statistical Analysis

SPSS 17.0 (SPSS Inc., Chicago, Illinois) was used for statistical analysis. The data were provided as a mean, standard deviation (SD), or percentage (%). If relevant, the t-test, paired t-test, and one-way ANOVA were used to analyze group differences. A P-value less than 0.05 was considered statistically significant.

Demographic characteristics of the study’s participant population

This study analyzed PT, INR, APTT and PFC levels in 40 PW with PBC during the first trimester, while also exploring the influence of age, BMI, blood type, and fetal sex on these coagulation parameters. Besides, 40 age-matched healthy PW were examined and served as a control group. The baseline demographic characteristics of the patients and controls that chose to participate in the study were shown in Table 1. The age of patients ranged between 18 and 40 years with a mean \(\pm\) SD of 29.6\(\pm\) 6.2 years. Patients less than 35 years of age made up 85% of the total patients. For controls, the age ranged from 17 to 41 years of age with a mean \(\pm\) SD of 28.2\(\pm\) 5.9 years. The control subgroups of less than 35 years made up 87.5% of the total control group. The average age of patients was slightly higher than the controls.

The patients were 35% (14) normal weight, 40% (16) overweight and 25% (10) obese, whereas the controls was 45% (18) normal weight, 35% (14) overweight and 20% (8) obese. These results show a predominant overweight or obese status in both patients and controls. There were no underweight participants. The patients were 65% (26) O+, 22.5% (9) A+, 10% (4) AB+, and 2.5% (1) AB-, whereas the controls was 37.5% (15) O+, 27.5% (11) B+, 20% (8) A+, 5% (2) AB+, 5% (2) O-, and 5% (2) B-. According to the data, the majority of the patients were O+, followed by A+. Similarly, the majority of the controls was O+, but much fewer than the patients, with B+ coming in second and A+ coming in third. There were no patients with blood types O-, B-, or B+, and no volunteers with blood type A-. Based on baby gender, 63% (25) of patients had male babies, whereas 45% (18) of the controls had girl babes.

Age-Related Variations on Coagulation Parameters in PW with PBC

Table 3 illustrates the impact of age groups on PT, INR value, APTT, and PFC controls and patients in the first trimester. Patients younger than 35 displayed significantly lower average PT and INR values than their age-matched controls. Similarly, patients aged 35 or older exhibited significantly reduced mean PT and INR values compared to their age-matched controls. Moreover, the mean PT and INR values were slightly lower in older patients (\(\geq 35\) years) than in younger patients (\(<35\) years). Analogously, controls aged 35 or older showed a minor decrease in mean PT and INR values compared to controls younger than 35 years old. The APTT and PFC mean values displayed significantly higher levels in patients aged \(\geq 35\) years compared to the controls of the same age group. Similarly, patients under 35 years old exhibited significantly higher average APTT and PFC values than their corresponding controls. Additionally, the mean APTT value in patients aged \(\geq 35\) years was slightly lower than in those under 35 years old. Analogously, the mean APTT value among controls aged \(\geq 35\) years showed a marginal decrease compared to controls under 35 years old. Patients aged 35 years or older displayed slightly elevated average PFC values compared to those younger than 35 years. A similar trend was observed in controls, where the mean PFC value for those aged \(\geq 35\) years was slightly higher than in controls aged \(<35\) years.

BMI-Related Effects on Coagulation Parameters in PW with PBC

The effects of BMI on PT, INR, APTT, and PFC in patients during their first trimester were summarized in Table 4. When BMI rises, the mean values of the PT, INR, and APTT tend to rise in both the controls and patients. However, when BMI increased, the mean value of the PFC decreased in both the controls and patients. The control group’s PT and INR mean values were significantly higher than the patients in three different categories of BMI (normal weight, overweight and obese PW). APPT and PFC, on the other hand, were significantly lower in three BMI control subgroups than in three BMI patient subgroups.

ABO Blood Group Impact on Coagulation Parameters in PW with PBC

Table 5 summarized the impacts of ABO blood group on PT, INR, APTT, and PFC in the controls and patients with PBC. All participants’ blood types were identified to investigate the effects of ABO blood group (O+, O-, A+, A-, AB-, AB+, B- and B+) on PT, INR, APTT, and PFC. As previously indicated, the majority of patients and controls (65% and 38%, respectively) had O+ blood type. Blood type A+ was found in 23% of patients and 20% of controls. The following blood types (O-, AB-, AB+, B- and B+) were present in extremely low numbers and were difficult to analyze; thus, they were grouped together. In our case-control studies, patients of all blood types exhibited markedly reduced average PT and INR values compared to controls across all blood types. Conversely, patients with all blood types showed significantly elevated mean APTT and PFC values compared to the corresponding control groups. Notably, there were no significant changes in mean PT, INR, APTT, or PFC values between blood types within the same group.

This study focused on PW residents in Jordan’s Al-Mafraq district who were receiving anticoagulant medication for PBC. In this study, clexane was preferred over warfarin or unfractionated heparin, and low-dose aspirin was also administered to PW with PBC. This approach aligns with the AHA recommendation to switch high-dosage warfarin treatment to clexane during the first trimester due to its fetal protection benefits [18]. Several previous studies support this recommendation, citing clexane’s advantages over unfractionated heparin during pregnancy, including longer half-life, weight-dependent dosing, reduced bleeding and osteoporosis risks, ease of non-intravenous administration and decreased monitoring requirements [2, 10, 11]. Additionally, in this study, we employed PT, INR and APTT, blood coagulation parameters to assess coagulation profiles in both our control group and patients with PBC who were administered a daily regimen of 40 mg of clexane and 75 mg of aspirin. In fact, INR depends on PT and is used to standardize anticoagulant monitoring, ensuring a consistent reference range for oral anticoagulant users. This aids in assessing sensitivity and variability during hypercoagulable pregnancies [11, 13, 14].

One notable finding in this study was that patients with PBC receiving clexane and aspirin treatment had mean PT and INR values of 11.8 seconds and 0.8, respectively, compared to controls, who had values of 13.8 seconds and 1.1, respectively. In comparison to controls, statistically speaking, patients had significantly lower mean PT and INR values in the first trimester. In the absence of anticoagulant treatment, most laboratories reported that the normal ranges for PT and INR in healthy adults were 10 to 13 seconds and 0.8 to 1.1, respectively [15, 18, 19]. Our controls’ PT and INR values were within the typical ranges for healthy adults. This is also compatible with the findings of a research conducted by Szecsi et al. [20], who found that PT and INR levels were generally constant during pregnancy, delivery, and postpartum, and they were within non-pregnant reference ranges. On the other hand, the observed PT and INR values for our patients were all at the lower end of the typical normal limits for healthy adults. It has been reported that the AHA advises individuals with clotting tendencies to target INR values between 3 and 4, while those at higher bleeding risk should aim for INR levels between 2 and 3. This recommendation also aligns with prior research [18, 21]. Besides, INR levels below the desirable range have been linked with an increased risk of DVT, whilst those above the desired range are connected with a significant risk of bleeding [15, 19]. Contrarily, our patients using 40 mg of clexane and 75 mg of aspirin daily had an INR of 0.8, which is below the suggested range for efficient anticoagulation. To stay within the AHA’s suggested INR range, it is best to gradually raise clexane dosage with careful physician supervision, with the goal of improving clexane’s safety and efficacy while lowering bleeding risk. However, because of the increased risk of bleeding during and after delivery, increasing daily clexane dose may result in negative effects such as postpartum hemorrhage in PW. To ensure a safe cesarean section and minimize bleeding risks during and after delivery, the American Society of Regional Anesthesia and Pain Medicine recommends maintaining an INR below 1.5. It is also recommended to stop using clexane 12 to 24 hours before the surgery [18].

Furthermore, thorough observations conducted on our patients at Al-Mafraq Hospital, spanning from pregnancy to delivery, indicated the absence of complications. These observations sparked a critical debate regarding adherence to AHA’s recommended range versus maintaining our prescribed daily dose of 40 mg of clexane and 75 mg of aspirin for patient safety and benefit. On light of these findings, it is necessary to reevaluate the appropriateness and safety of the AHA’s suggested INR range (2-3) for our specific group of patients [18]. It is possible that Middle Eastern women might not benefit from the INR range (2-3) recommended by the AHA. Therefore, when implementing these recommendations in clinical practice, it is essential to take both environmental and hereditary variables into account and make sure they are consistent with the characteristics of the target population under consideration

Based on our study’s APTT data, the average APTT for the control group was 31.2 seconds, while the average APTT for the patient group was 34 seconds. The mean APTT value for patients was significantly higher compared to controls. Prior investigations has determined that the APTT reference range for individuals without health issues is 30-40 seconds. For patients undergoing anticoagulant treatment, the reference range is 1.5-2.5 times the control value, equivalent to 60 to 80 seconds [22, 23]. In line with the reference range, the control group’s mean APTT was closer to the lower limit of normal. More importantly, the results of this study revealed that patients who are taking anticoagulants have considerably lower APTT readings than the stated reference range and APTT value fell within the middle of the range of normal individuals. Previous study revealed that APTT prolongation often arises in patients receiving high warfarin doses or low molecular weight heparin such as clexane [12]. Although a statistical difference exists between the control group and the patients, it can be inferred that the administration of both clexane and aspirin has minimal impact on the APTT in our patient population. Prior research has shown significant coagulation factor level variations in pregnancy, resulting in approximately double the coagulation activity compared to non-PW, termed a hypercoagulable state [1, 2, 20]. This phenomenon may help elucidate the observed low APTT values in our patient cohort.

It is important to keep in mind that a normal APTT may not always rule out mild coagulation disorders in certain patients, necessitating supplementary tests. APTT assesses general clotting factor function, potentially masking mild deficiencies in specific cases where one factor’s temporary elevation obscures another’s deficiency [6, 22, 23]. When APTT shows unexplained abnormalities, precise interpretation is vital, prompting further investigation. It has been reported that PT measures extrinsic activation times and common pathways, while APTT evaluates intrinsic and common pathway. The common pathway involves X, V, II, thrombin, and fibrinogen (Factor I) [2, 9]. Fibrinogen is a 340 kDa hexameric glycoprotein that is primarily produced by hepatocytes. It is a crucial structural and functional component of blood clotting. A growing body of research highlight an increased risk of fibrinogen-induced thrombosis, particularly in females. Fibrinogen was found to exhibit diverse roles within the hemostasis system and can also be synthesized extracellularly in tissues such as lung and kidney [2, 9, 12, 16]. Moreover, because fibrinogen is involved in the production of thrombi, this study sought to assess PFC levels in PW with PBC. The results of the study demonstrates a significant difference in mean PFC between the control group (3.8 g/L) and patients with PBC (5.1 g/L). The standard reference range for adult women generally spans 1.5 to 3.5 g/L, with laboratories advised to establish specific ranges [12, 16, 24]. In our study, the mean value of PFC within the control group measures at 3.8 g/L, a value slightly exceeding the upper boundary of the predetermined acceptable range. Notably, the mean PFC level in our patients was 5.1 g/L, which exceeded the upper reference limit. These results are consistent with earlier research linking fibrinogen levels exceeding 4.145 g/L with DVT, which is pertinent to PBC [25]. On the other hand, [26] observed that higher PFC are associated with an increased risk of pulmonary embolism when paired with DVT, but not when DVT is present alone.

[27] observed that during a typical pregnancy, there was a shift towards increased blood clotting tendencies, reducing the risk of bleeding during childbirth. This shift involved elevated fibrinogen levels, a mild reduction in APTT and an INR value below 0.9. In a similar vein, multiple studies have linked lower PT, INR and APTT values in PW to elevated intrinsic pathway coagulation factors such as fibrinogen and prothrombin. These factors contribute to a hypercoagulable state, potentially affecting female-specific conditions like PBC during pregnancy. Furthermore, these studies have found a clear link between higher fibrinogen levels and enhanced platelet aggregation and clotting tendencies, which correlates with a higher likelihood of clotting episodes [1,2,3,7,8,9,10,11,13,14,15,16,17,18,19,20,23]. These findings suggest that increased fibrinogen levels enhance platelet aggregation and clotting while decreasing PT, INR, and APTT. Conversely, decreased fibrinogen levels lead to prolonged PT and APTT, along with elevated INR due to impaired clotting. Collectively, these studies propose that parameters such as PT, INR, and APTT can serve as indicators of variations in coagulation proteins. Based on prior research and our findings, higher fibrinogen levels in our patients likely played a role in PBC formation, while also lowering PT, INR, and APTT. Our findings suggest that elevated PFC in our PBC patients may have led to PBC formation while lowering PT, INR, and APTT. However, further research is needed to pinpoint the underlying factors driving this notable increase in PFC levels among our PBC patients.

The effects of age, BMI, blood types, and fetal sex on clotting parameters (PT, INR, APTT) and PFC were assessed in PW with PBC. Statistically significant differences between patients and controls persisted even after adjusting for age. Interestingly, in patients aged \(\geq 35\) years, PT and INR were lower, while PFC were significantly higher compared to patients aged \(<35\) years. These findings suggest a potential association between high PFC and shorter PT and INR in patients aged \(\geq 35\). In line with our discovery, a prior investigation demonstrated that maternal age and lifestyle choices could influence PBC development. PBC incidence rises over four times in women above 35 years compared to younger counterparts [16]. Our findings are also consistent with the fact that PFC levels tend to rise with age, presumably contributing to the increased risk of venous thromboembolism found in the elderly [5, 28]. Besides, our data revealed that there were no significant differences in BMI between the control and patient groups, and higher BMI values were associated with increased PT, APTT, and INR across all subgroups. Hypertension, often associated with high BMI, is a major risk factor for cardiovascular diseases and was linked to elevated clotting parameters [29]. Recently, [30] documented a case of heparin-induced thrombocytopenia in a PW who was obese and had venous thrombosis [30]. This study also examined the impact of blood type on clotting parameters, mainly focusing on patients with blood type O+. However, no significant variations were observed across different blood types. Similarly, gender had no significant influence on clotting parameters in both patient and control groups. Therefore, adapting these variables or factors is essential for accurate coagulation assessment in blood-related disease patients. While the effects of these variables remain unclear, it is crucial to understand the complex interplay of these factors during pregnancy to grasp PBC fully. These findings underscore the need to consider various factors affecting coagulation parameters, such as anticoagulant types, dosage, and patient characteristics.

This study exhibits certain limitations. The first limitation is the relatively small sample size. The study included forty PW with PBC and an equal number of age-matched controls. While this sample size was sufficient to detect significant differences in clotting parameters between the two groups, a larger sample size would have provided more statistical power and increased the generalizability of the findings. The second, The PT, INR, and APTT tests were primarily designed to assess plasma elements and may not adequately evaluate clinical coagulopathy like PBC. Various confounding factors, including genetics, nutrition, medications, diseases (vascular/liver), bacterial presence, reagent variability, blood attributes (volume, plasma dilution, citrate concentration), anticoagulant dosage, coagulation factor deficiencies, alcohol consumption, and vitamin K insufficiency, can impact the accuracy of PT, INR, APTT and PFC assessments in blood-related diseases [1, 4, 8, 18, 19, 22]. To ensure precise coagulation evaluation, it is crucial to consider these factors. Therefore, the third drawback is that the study did not evaluate these potential confounding factors that might impact clotting properties, emphasizing the need of taking these factors into account for meaningful test findings. In light of the aforementioned limitations and considering the findings presented above, the use of clexane for treating PBC in PW, particularly within the context of Jordan, remains advisable. Nonetheless, to bolster the validity and reliability of our study’s results, future research endeavors should encompass larger and more diverse participant samples, coupled with a thorough examination of confounding factors.

This study represents the initial investigation in Jordan, comparing coagulation parameters (PT, INR, APTT, and PFC) between PW with PBC treated with 40 mg/day of clexane and 75 mg of aspirin daily, and a control group of healthy PW. Results showed that in the first trimester, PW with PBC had significantly lower mean PT and INR readings compared to controls, while mean APTT and PFC values were significantly higher. Importantly, PW with PBC using 40 mg/day of clexane had a mean INR value of 0.8, below the therapeutic range, suggesting a potential for dose adjustment. Nonetheless, PW with PBC safely delivered their babies with the prescribed doses of clexane and aspirin.

The study looked at the impacts of maternal age, BMI, blood type, and fetal sex on coagulation profiles, and found that maternal age and BMI had relatively minor effects. The study also highlighted the role of PFC in clotting and its potential link to PBC, but the exact cause of elevated PFC remained unclear, warranting further investigation. It is important to note that PT, INR, and APTT are influenced by various factors in the clotting cascade, emphasizing the need for a comprehensive assessment of clotting factors. This study has clinical implications for diagnosing and managing PW with PBC and the efficacy of anticoagulant treatment. Additionally, it advances our understanding of blood clotting factors, particularly fibrinogen, in PBC disorder. Therefore, PW with PBC requiring anticoagulant therapy should receive careful monitoring and treatment.

The authors would like to thank the pregnant women who took part in this study for their devotion throughout the trial. The authors would also want to express their gratitude to all staff members at the Obstetrics, Gynecology, and Pediatrics hospital in Al-Mafraq, Jordan, who assisted in the completion of this study.

This research paper received no external funding.

The authors declare no conflicts of interest.

All authors contributed equally to this paper. They have all read and approved the final version.

Informed consent was obtained from all participates in the study as needed.

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