Introduction And Physiology

• Bleeding in a neonate is a life-threatening medical emergency.
• The primary survey is bypassed to prioritize immediate stabilization if shock or severe anemia is present.
• A stable venous access must be secured urgently, and blood products must be arranged.
• Neonates have significant quantitative and qualitative developmental differences in their hemostatic system.
• Neonatal platelets are generally hyporeactive compared to adults.
• Despite hyporeactive platelets, the primary hemostasis is faster in neonates. The bleeding time is shorter, possibly due to higher von Willebrand factor levels and elevated hematocrit.
• Secondary hemostasis shows decreased levels of Vitamin K-dependent coagulation factors and contact factors.
• This translates to a physiologically prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) in neonates.
• The overall hemostatic system in healthy neonates is well-balanced. However, systemic diseases easily tilt this balance and result in clinical bleeding.

Clinical Evaluation

A systematic clinical evaluation must run parallel to emergency stabilization.

History

• Obtain a detailed maternal history. Look for maternal illnesses such as systemic lupus erythematosus or immune thrombocytopenia.
• Inquire about maternal medications during pregnancy. Aspirin, anticonvulsants, and antitubercular drugs can predispose the neonate to bleeding.
• Take a thorough family history of bleeding disorders.
• Obtain a birth history to rule out perinatal asphyxia or significant birth trauma.

Physical Examination

• Assess the general appearance. Determine if the neonate is sick-looking or well-looking.
• Characterize the type of bleeding. Determine if the bleeding is localized to a specific organ or generalized across multiple sites.
• Examine the abdomen for hepatosplenomegaly, which may suggest congenital infections or liver disease.
• Note the sex of the baby. Severe hemophilia primarily affects male neonates.

Diagnostic Investigations

Any neonate with a bleeding disorder should undergo baseline laboratory investigations. Samples should be drawn from a venous source, and capillary samples must be avoided.

Level 1 Investigations

• Complete blood count with platelet count.
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT).
• Fibrinogen and D-dimer levels, particularly in sick neonates.

Level 2 Investigations

• Peripheral smear to evaluate the differential diagnosis of thrombocytopenia.
• Human platelet antigen analysis if neonatal alloimmune thrombocytopenia is suspected.
• Single clotting factor assays based on the PT and aPTT constellation.
• Mixing studies, which are useful in the presence of factor inhibitors.

Level 3 Investigations

• Platelet function analysis or platelet aggregometry.

The Apt Test (Alkali Denaturation Test)

• This test differentiates swallowed maternal blood from fetal gastrointestinal bleeding.
• Mix one part of the bloody stool or vomitus with five parts of sterile water.
• Centrifuge the mixture for 2 minutes to separate the clear pink supernatant (hemolysate).
• Add 1 mL of 1% sodium hydroxide to 4 mL of the hemolysate.
• Adult hemoglobin changes from pink to yellow-brown, indicating maternal blood.
• Fetal hemoglobin is resistant to alkali and stays pink, confirming fetal bleeding.

Algorithmic Interpretation Of Coagulation Profile

The interpretation of the coagulation profile must always be correlated with the clinical status of the neonate.

Etiological Classification Of Bleeding

Disorders Of Primary Hemostasis

• These disorders involve defects in platelet number or function.
• Increased destruction of platelets: Can be nonimmune (sepsis, necrotizing enterocolitis, asphyxia, hemangioma) or immune (fetal and neonatal alloimmune thrombocytopenia, maternal immune thrombocytopenia).
• Decreased production of platelets: Caused by maternal pregnancy-induced hypertension, bone marrow infiltration, or congenital megakaryocytic thrombocytopenia.
• Platelet function disorders: Includes Glanzmann's thrombasthenia and Bernard-Soulier syndrome.

Disorders Of Secondary Hemostasis

• Acquired coagulation disorders: Includes Vitamin K deficiency bleeding, acute liver failure, gestational alloimmune liver disease, and disseminated intravascular coagulation.
• Inherited coagulation disorders: Includes Hemophilia A (Factor VIII deficiency), Hemophilia B (Factor IX deficiency), and severe von Willebrand disease.

General Management Principles

• Ensure the airway, optimize breathing, and support circulation.
• Nurse the baby in a thermoneutral environment and start oxygen if needed.
• Correct underlying metabolic derangements like hypoglycemia, hypocalcemia, and hypokalemia.
• Vitamin K: Administer 1 mg intravenously or intramuscularly if it was not received at birth or if the status is unknown.
• Fresh Frozen Plasma (FFP): Administer 15 to 20 mL/kg for significant or active bleeding. Repeat every 8 to 12 hours if needed.
• Platelet Transfusion: Use restrictive thresholds. Transfuse for active bleeding or if the platelet count falls below critically low thresholds defined by unit protocols.
• Packed Red Blood Cells (PRBC): Administer PRBC or whole blood in cases of severe acute blood loss. Ensure pretransfusion diagnostic samples are collected before transfusion.

Management Of Specific Conditions

Fetal And Neonatal Alloimmune Thrombocytopenia (FNAIT)

• It is the most common cause of severe, life-threatening thrombocytopenia in neonates.
• The mother lacks a specific human platelet antigen that the fetus possesses. Maternal antibodies cross the placenta and destroy fetal platelets.
• The mother is typically asymptomatic with a normal platelet count.
• Perform a cranial ultrasound immediately to rule out intracranial bleeding.
• For platelet counts less than 30,000, administer random donor platelets along with intravenous immunoglobulin (IVIG).
• IVIG is administered at a dose of 1 g/kg/day for 2 days.
• For platelet counts between 30,000 and 50,000, IVIG alone is indicated.

Vitamin K Deficiency Bleeding (VKDB)

• Early VKDB: Occurs within the first 24 hours of life. It is commonly due to maternal medications like anticonvulsants or antitubercular drugs.
• Classic VKDB: Occurs between 1 and 7 days of life. It is caused by a lack of prophylactic Vitamin K at birth and poor enteral feeding.
• Late VKDB: Occurs between 1 and 8 weeks of life. It is associated with fat malabsorption syndromes like biliary atresia and liver disorders.
• Diagnosis is confirmed by prolonged PT and aPTT, with rapid normalization of PT after Vitamin K administration.
• Treatment involves intravenous Vitamin K. Clinical bleeding typically decreases within 20 minutes of injection.

Disseminated Intravascular Coagulation (DIC)

• DIC occurs due to the failure of coagulation regulation. It results in uncontrolled thrombin generation, widespread fibrin deposition, and consumption of coagulation factors.
• It presents as massive, life-threatening hemorrhage from puncture sites or the gastrointestinal tract.
• Common triggers include sepsis, perinatal asphyxia, necrotizing enterocolitis, and severe prolonged hypothermia.
• Management is directed at correcting the triggering disease.
• Treatment requires replacing depleted factors with FFP, cryoprecipitate, and platelet transfusions.