Disorders of platelets

1

What is pseudothrombocytopenia?

Pseudothrombocytopenia, or spurious thrombocytopenia, is a falsely low automated platelet count that occurs secondary to in vitro platelet clumping. This is generally an incidental finding in an otherwise asymptomatic patient and can be confirmed by observation of platelet clumping on the peripheral smear. Pseudothrombocytopenia can be caused by a poorly collected specimen that has clotted, the presence of ethylenediaminetetra-acetic acid (EDTA)–dependent antibodies against platelets, or platelet satellitism (platelets around neutrophils or monocytes). An accurate platelet count can be obtained by doing a manual count on a freshly collected sample or by collecting the sample in a tube with a different anticoagulant, such as citrate.

2

Differentiate the signs and symptoms of bleeding secondary to a platelet disorder from that of a coagulation disorder.

Bleeding because of a platelet disorder typically consists of skin and mucous membrane bleeds, such as petechiae, small ecchymoses, gum bleeding, epistaxis, gastrointestinal (GI) bleeding, and menorrhagia. Petechiae is a rather specific finding for thrombocytopenia and should prompt checking a platelet count. Deep subcutaneous muscle and joint bleeds are more characteristic of coagulation disorders, although they can also occur in rare disorders of platelet dysfunction.

3

Discuss the mechanisms and causes of thrombocytopenia in the newborn.

Mechanisms of thrombocytopenia in the newborn can be broadly categorized as those with decreased bone marrow production, increased peripheral destruction, or consumption. In many conditions, it is not easy to delineate the exact mechanism, and a combination of mechanisms occurs. The best approach to identify the etiology is to look for the most common causes in the particular setting, whether the infant is well or sick, and search for any relevant maternal factors and significant family history. Box 8.1 enumerates the many possible causes of neonatal thrombocytopenia.

4

What is the treatment for neonatal thrombocytopenia?

Except in cases of maternal autoimmune thrombocytopenia, platelet transfusion with cytomegalovirus-negative, white blood cell (WBC)–depleted platelet concentrate remains the treatment of choice for severe thrombocytopenia in the neonate. The primary aim for platelet transfusion is to maintain a platelet count that will prevent the risk of significant hemorrhage, particularly intracranial bleeding.

There is no general consensus as to a “safe” platelet count in the neonate and no true “threshold” that should be maintained because lower platelet count is not a strong predictor of increased bleeding. Gestational age less than 34 weeks, early-onset severe thrombocytopenia (in 10 days from birth), sepsis, and illnesses like necrotizing enterocolitis are factors for increased risk of bleeding events and may be conditions where vigilance for increased bleeding risk should be maintained and platelets transfused based on clinical concern. A randomized controlled trial that compared platelet transfusion thresholds in preterm infants with severe thrombocytopenia noted that a higher rate of death or major bleeding was seen within 28 days after randomization in patients assigned to receive platelet transfusions at a platelet-count threshold of 50 × 10 ⁹ /L, as opposed to those at 25 × 10 ⁹ /L. A dose of 10 mL/kg of platelet concentrate should raise the platelet count to 75 × 10 ⁹ /L to 100 × 10 ⁹ /L.

5

Define neonatal alloimmune thrombocytopenia (NAIT).

NAIT is thrombocytopenia in the neonate resulting from immune-mediated platelet destruction caused by alloantibodies produced and transferred by the mother against a specific fetal platelet antigen that the baby inherited from the father and that is absent in the mother.

This is the platelet equivalent of Rh hemolytic disease of the newborn, although it can occur during the first pregnancy. This should be suspected in an otherwise healthy full-term newborn with no other obvious causes for thrombocytopenia who presents with petechiae, GI bleeding, or, in as many as 20% of cases, intracranial hemorrhage. The diagnosis is confirmed by determination of platelet alloantigen phenotype of the parents and detection of maternal antibody with specificity for paternal or fetal platelet antigen. The most common platelet antigen involved is the human platelet antigen (HPA)-1a, or HPA-4 in those of Asian background.

6

Discuss the management of NAIT.

NAIT is a self-limiting condition with eventual recovery of the platelet count in 2 to 4 weeks. Until the platelet count recovers, however, the neonate is at an increased risk for life-threatening hemorrhage because of severe thrombocytopenia in the immediate newborn period. It is recommended that infants with NAIT be transfused to maintain a platelet count greater than 30 × 10 ⁹ /L in the absence of bleeding, and higher based on clinical bleeding symptoms. The gold standard of treatment is transfusion with maternal platelets; however, this is often not a practical option. If transfusions are needed, then random donor platelets can be given and HPA-1a can be requested. Additionally, intravenous immunoglobulin (IVIG) 1 gram/kg for 1 to 2 days can be given along with random donor platelets. Antenatal management should be considered for subsequent at-risk pregnancies in conjunction with high-risk obstetric care.

7

Differentiate neonatal autoimmune thrombocytopenia (NITP) from NAIT.

In NITP, immunoglobulin G (IgG) autoantibodies from the mother who has an underlying immune thrombocytopenia or other autoimmune diseases, such as systemic lupus erythematosus, are passively transferred to the baby who may subsequently develop thrombocytopenia secondary to immune destruction of platelets. The antibodies are directed against antigens common to both mother and baby, unlike in NAIT, in which the antibodies are only directed against the baby’s platelets. Therefore in NITP, the mother has a low platelet count, whereas in NAIT, maternal platelet count is normal. The platelet count in NITP can be normal at birth, with nadir at 2 to 5 days after delivery. Bleeding problems in utero or during delivery are rare. This is also a self-limiting condition, with platelet recovery in 2 to 3 months. Treatment options in cases of severe thrombocytopenia (< 50 × 10 ⁹ /L) include IVIG and corticosteroids.

8

What is the differential diagnosis of acquired thrombocytopenia in children?

• a.

  Destruction (i.e., immune- or nonimmune-mediated)

• b.

  Sequestration (i.e., hypersplenism)

• c.

  Dilution (i.e., massive transfusion)

• d.

  Decreased production (i.e., bone marrow infiltration, injury, or failure)

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