thrombocytopenia due to platelet alloimmunization

Thrombocytopenia due to platelet alloimmunization is a condition where the immune system produces antibodies against the platelets, leading to their destruction and a subsequent decrease in platelet count. This can occur when there is an incompatibility between the mother's platelets and the father's platelets, resulting in the mother's immune system attacking the fetus's platelets.

Causes:

• Incompatibility between the mother's platelets and the father's platelets [4]
• Alloimmunization to HPA antigens has been reported in 2% to 8% of multiply transfused thrombocytopenic patients [3]

Symptoms:

• Severe bleeding, including intracranial hemorrhage, in the fetus or neonate [6]
• Thrombocytopenia in a newborn with HDN can also be due to concomitant alloimmunization of the mother against a PLT-specific antigen such as HPA-5b [5]

Definition:

• Neonatal alloimmune thrombocytopenia (NAIT) is a rare disorder that can lead to severe bleeding in the fetus or neonate [6]
• Thrombocytopenia in a neonate is defined as a platelet count of less than 150 x 10^9/l and is considered severe if the platelet count falls below 50 x 10^9/l [7]

Other information:

• Platelet alloimmunization can also occur due to transfusion of incompatible platelets, leading to refractoriness to platelet transfusions [1]
• The HPA system has less antigenic variability when compared with the HLA system, which may be why far fewer antibodies against HPA are implicated in immune-based platelet refractory cases [3]

References: [1], [3], [4], [5], [6], [7]

Thrombocytopenia due to platelet alloimmunization, also known as Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT), is a condition where the mother's immune system produces antibodies against the fetus's or newborn's platelets. This can lead to a significant decrease in platelet count, resulting in various signs and symptoms.

Common Signs of FNAIT:

• Petechiae: small red or purple spots on the skin [9]
• Purpura: larger areas of bleeding under the skin [1]
• Bruising: easy bruising due to low platelet count [5]

These signs are often observed in newborns with FNAIT, and can be a result of the mother's immune system attacking the fetus's or newborn's platelets.

Other Symptoms:

• Cephalohematoma: bleeding under the scalp [9]
• Hematomas: large bruises on the skin
• Melena: blood in stool
• Hemoptysis: coughing up blood
• Retinal bleeding: bleeding in the eyes
• Hematuria: blood in urine

These symptoms can range from mild to severe, and may be accompanied by other complications such as internal bleeding.

Important Note: Mildly affected infants may be asymptomatic, while those with severe thrombocytopenia may experience more pronounced symptoms [5].

References:

[1] Common signs include petechiae (small red or purple spots on the skin), purpura (larger areas of bleeding under the skin), and bruising.

[5] Mildly affected infants may be asymptomatic. In those with severe thrombocytopenia, the most common presentations are petechiae, purpura or cephalohematoma at birth.

[9] Common Signs of FNAIT · Petechiae: typically reddish, pinpoint spots on the skin · Purpura: larger, purplish skin discolorations · Cephalohematoma: bleeding under the scalp.

Thrombocytopenia due to platelet alloimmunization can be a challenging condition to diagnose, but several diagnostic tests can aid in the identification of this condition. Here are some of the key diagnostic tests used to diagnose thrombocytopenia due to platelet alloimmunization:

• Complete Blood Count (CBC): A CBC is often the first test ordered to evaluate thrombocytopenia. It measures the number of platelets, red blood cells, white blood cells, and hemoglobin in the blood.
• Reticulocyte count: This test measures the number of young red blood cells in the blood, which can indicate whether the bone marrow is producing enough new red blood cells to replace those being destroyed.
• Peripheral smear examination: A peripheral smear is a blood test that examines the shape and size of red and white blood cells. It can help identify abnormalities in platelet morphology.
• Coagulation screen: This test evaluates the blood's ability to clot, which can be affected by thrombocytopenia due to platelet alloimmunization.
• Liver function tests: These tests evaluate liver function, as liver disease can cause thrombocytopenia.

In addition to these general diagnostic tests, specific tests can be used to diagnose platelet alloimmunization:

• Indirect platelet immunofluorescence test: This test detects the presence of anti-platelet antibodies in the blood.
• Monoclonal antibody immobilization platelet assay (MAIPA): This test is a sensitive and specific method for detecting anti-platelet antibodies.

These tests can help diagnose thrombocytopenia due to platelet alloimmunization, but it's essential to consider the clinical context and other laboratory results when interpreting these findings.

References:

• [1] Cohn CS. (2020) A screening test should be ordered to confirm alloimmunization to platelets.
• [11] Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal alloimmunization to a paternally inherited fetal platelet antigen (HPA), and can occur in first pregnancies. Maternal alloantibodies cross the placenta, resulting in fetal thrombocytopenia, which can be associated with severe bleeding such as intracranial hemorrhage (ICH) 3.
• [14] These would include: (1) a platelet count <100 × 10^9/L, with the exclusion of other causes of thrombocytopenia; (2) a low platelet count nadir (<20 × 10^9/L); (3) a platelet count response to therapy (corticosteroids, IVIG, or treatment of the underlying secondary cause); and (4) a positive anti-platelet autoantibody test.

Thrombocytopenia due to platelet alloimmunization can be challenging to treat, but various drug treatments have been explored to manage this condition.

• Immunosuppressive agents: Immunosuppressive agents such as IVIG (Intravenous Immunoglobulin) can provide short-term benefit in patients with platelet refractoriness resulting from alloimmunization [2]. These agents work by suppressing the immune system's response against the platelets.
• Eltrombopag: Eltrombopag is a thrombopoietin receptor agonist that has been shown to increase platelet counts in patients with chronic immune thrombocytopenia (ITP) [8]. It works by stimulating the production of platelets in the bone marrow.
• Avatrombopag: Avatrombopag is another thrombopoietin receptor agonist that has been found to be effective and safe for treating refractory platelet transfusion refractoriness (PTR) patients [4]. It also works by stimulating the production of platelets in the bone marrow.
• Eculizumab: Eculizumab is a monoclonal antibody that has been shown to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization [6]. It works by inhibiting the complement system, which plays a role in the immune response against platelets.
• Corticosteroids and immunoglobulins: Corticosteroids and immunoglobulins are also used to treat thrombocytopenia due to platelet alloimmunization. These medications can help reduce the immune system's response against the platelets [9].

It is essential to note that these drug treatments may have varying degrees of success, and individual patient responses may differ. A comprehensive treatment plan should be developed in consultation with a healthcare professional.

References: [2] Immunosuppressive agents such as IVIG can provide short-term benefit in patients with platelet refractoriness resulting from alloimmunization. [4] Avatrombopag is an effective and safe treatment option for refractory PTR patients. [6] Our study suggests that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. [8] Eltrombopag is currently approved for ITP, HCV-related thrombocytopenia, and other conditions. [9] Corticosteroids and immunoglobulins are used to treat various immune-mediated disorders.

Differential Diagnosis of Thrombocytopenia Due to Platelet Alloimmunization

Thrombocytopenia, a condition characterized by abnormally low levels of platelets in the blood, can result from various causes. One such cause is platelet alloimmunization, which occurs when there is an incompatibility between the mother's platelets and the father's platelets. This condition can lead to severe thrombocytopenia, making it essential to establish a differential diagnosis.

Causes of Thrombocytopenia

Thrombocytopenia can result from either decreased production or increased destruction of platelets. The decision to transfuse platelets is a combination of the patient's clinical presentation and laboratory results [6]. In cases where thrombocytopenia is suspected due to platelet alloimmunization, it is crucial to consider other potential causes.

Differential Diagnosis

The differential diagnosis for thrombocytopenia includes:

• Sepsis/Infection: Sepsis can lead to thrombocytopenia by causing a systemic inflammatory response that affects the bone marrow's ability to produce platelets [5].
• Perinatal Hypoxia: This condition can result from inadequate oxygen supply during birth, leading to thrombocytopenia in newborns [9].
• Intrauterine Growth Restriction (IUGR): IUGR can cause thrombocytopenia due to the fetus's reduced growth and development [5].
• Prematurity: Premature infants are at a higher risk of developing thrombocytopenia due to their immature bone marrow function [9].
• Necrotizing Enterocolitis (NEC): NEC can cause thrombocytopenia in newborns by leading to inflammation and damage to the intestinal tract [5].
• Bone Marrow Failure: This condition can result from various causes, including chemotherapy, radiation therapy, or bone marrow disorders, leading to decreased platelet production [13].

Immature Platelet Fraction (IPF)

The immature platelet fraction (IPF) is a marker that indicates the percentage of immature platelets in relation to the total PLT count. It has been shown to be effective in differentiating between thrombocytopenia due to bone marrow failure and other causes [14].

Conclusion

In conclusion, differential diagnosis of thrombocytopenia due to platelet alloimmunization requires careful consideration of various potential causes. By understanding the underlying mechanisms and using diagnostic markers such as IPF, healthcare providers can accurately diagnose and manage this condition.

References:

[5] Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS) Clinical presentation and diagnosis of heparin-induced thrombocytopenia; Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity; Clinical use of ginkgo biloba; Diagnostic approach to anemia ...

[6] Thrombocytopenia is defined as a low circulating platelet count (<150,000 per microliter). Platelet life span is normally approximately 5 days, with continual renewal. Thrombocytopenia results from either a reduced production of platelets in the bone marrow, increased clearance, sequestering of platelets in the spleen, or dilution.

[9] *The pathogenesis of thrombocytopenia is often multifactorial. Thrombocytopenia associated with neoplasia, infectious disease, liver disease, and drug administration often has a complex mechanism with multiple contributing factors. Editor's note: This article was originally published in June 2020 as "Differential Diagnosis: Thrombocytopenia"

[13] IPF related parameters showed high efficacy in the differential diagnosis of thrombocytopenia. However, due to the small numerical values of the IPF related parameters in some thrombocytopenia patients, the fluctuations of IPF% and H-IPF% should also be taken into consideration. Though H-IPF% is a new parameter, its effectiveness in the ...