An educational, fictional case report recently published in Academic Pathology described the first pregnancy of a 27-year-old woman who received minimal prenatal care and whose newborn was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT).
The primary objective of the case study was to identify examples of the following pathogenic categories of thrombocytopenia:
- Decreased production of platelets
- Decreased survival of platelets
- Platelet sequestration, in which platelets are removed from circulation but are not destroyed
- Dilutional thrombocytopenia, in which a decrease in platelet counts is observed because of additional large volumes of fluid; this frequently occurs during a blood transfusion
Delivery and initial examination of the newborn
The pregnant patient presented to triage in labor. She gave birth to a male newborn via a vaginal delivery at 39 weeks’ gestational age.
Examination of the baby revealed petechial hemorrhages spread diffusely on his back, chest, and limbs. Additionally, bruising was observed across his anterior and lateral chest, which involved approximately 15% of the chest. Mucocutaneous purpura were seen as well, specifically on the lower labial mucosa and the right buccal mucosal.
Read more about FNAIT prognosis
What is the differential diagnosis for this infant?
“Petechial hemorrhages, bruising and purpura are all signs of defective hemostasis,” the authors wrote. A differential diagnosis needs to be formulated, taking into consideration the various etiologies and types of defective hemostasis.
Primary hemostasis is initiated with endothelial injury, which leads to neural reflex stimulation and the release of endothelins. This, in turn, is associated with vasospasm from the neural stimulation and transient vasoconstriction of the blood vessels affected. Taken together, these responses decrease blood flow and increase platelet accumulation in vessel walls. Blood vessel injury exposes von Willebrand factor (vWF), which leads to subsequent platelet activation and aggregation.
In secondary hemostasis, activation of the coagulation cascade stabilizes the platelet plug and helps to more effectively stop the bleeding. Fibrinogen, which is activated by thrombin, forms fibrin. The process of fibrinolysis regulates hemostasis by preventing the growth and pathologic development of blood clots.
Defective primary hemostasis may be due to issues with platelets, including defects in production, increased destruction, sequestration, and dilution, along with qualitative platelet defects. Non-platelet causes, such as defects in fibrinogen or vWF, may disturb primary hemostasis as well.
In situations of defective hemostasis, many overlapping findings are seen on physical examination. Petechiae are associated with the leakage of blood from small blood vessels; bruising is linked to subcutaneous hematomas due to vascular damage. The presentation in this patient, which suggests a bleeding disorder, requires additional workup to determine the correct diagnosis.
Appropriate laboratory tests for the mother and the baby
Initial workup when bleeding is a concern includes a complete blood count (CBC), reticulocyte count, vitamin K level, type and screen, haptoglobin, direct antiglobulin test (DAT), fibrinogen, prothrombin time (PT), and partial thromboplastin time (aPTT). CBC involves hemoglobin, hematocrit, red blood cell (RBC), white blood cell, and platelet counts.
Coagulation studies, such as PT and aPTT, evaluate patients for defective secondary hemostasis. Other assessments include fibrinogen levels; seeking features of mucosal, skin, and deep tissue bleeding; and family history of bleeding disorders. Brain imaging via computed tomography (CT) may be performed to rule out the presence of life-threatening intracranial bleeding.
Blood typing and antibody screening for RBC antibodies is important in cases of neonatal bleeding. Studies designed to evaluate platelet dysfunction can be performed as well.
Maternal blood type, CBC, and antibody screening also are performed. Neonatal blood type, CBC, DAT, reticulocyte counts, fibrinogen level, and coagulation studies are carried out. A head CT scan reveals a resolving small parenchymal hemorrhage on the infant’s head.
Findings in the mother and the baby
The infant’s test results show thrombocytopenia; the mother has normal laboratory findings. Mother and baby have incompatible Rhesus D (RhD) blood types, and the mother exhibits a negative antibody screen. A prioritized differential diagnosis should be created based on the infant’s laboratory test results.
Hemolytic disease of the fetus and newborn (HDFN) is ruled out. The infant and his parents undergo testing for platelet antigen incompatibility, platelet alloantibodies, and human platelet antigen (HPA) genotypes.
High suspicion for FNAIT is noted in this infant because of his isolated severe thrombocytopenia and test findings indicative of a bleeding disorder.
Although FNAIT is considered to be the “platelet counterpart of HDFN,” a key difference is that, unlike in severe HDFN, approximately 50% of cases of FNAIT are reported in an initial pregnancy “due to transplacental transport of fetal platelets.”
“Treatment for [F]NAIT includes [intravenous immunoglobulin] IVIG[,] as well as random donor platelets as the first-time platelet product,” the authors concluded.
