EtiologyA.Deficiency of clotting factors:1.Transitory deficiencies-Deficiency of vitamin K dependent C.F- II, VII, IX, X. Deficiency of anticoagulant proteins C & S.
Causes:a. Total parenteral nutrition or antibioticsb. Lack of administration of vitamin K .c. Drug intake in pregnancy eg.i. Phenytoin, Phenobarbital, Salicylates . (Interferes with the synthesis of vit. K dependent c.f. ) ii. Calmodulin compounds : interfare with synthesis of vit K dependeat C.F.
• The incidence among babies born to mothers on these drugs have varied between 6-12%*. In a recent series on children born to mothers on anticonvulsants, abnormal PT was documented in 14 out of 105 babies (13%) , no overt bleeding was observed*.
2. Disturbances of clotting- Related to DIC due to infection, shock, anoxia, NEC, renal vein thrombosis, use of IV canula.3. Inherited abnormalities of C.F. a. X-Linked recessive diseases- i. Hemophilia-A : Factor VIII deficiency. ii. Hemophilia-B : Factor IX deficiency.
b. Autosomal dominant diseases: i. Von Willebrand disease – Deficiency of VWF which is a carrier of factor VIII & as a platelet aggregation agent.c. Autosomal recessive diseases: i. Severe factor VII & factor XIII deficiency – intracranial hemorrhage in neonates ii. Factor XI deficiency – unpredictable bleeding during surgery/trauma.
iii. VWD Type IIIB. Platelet problems:1. Qualitative disorders:- Glanzman’s thrombasthenia.- Bernard-Soulier syndrome- Platelet type VWD
2. Quantitive disorders:- Immune thrombocytipenia- Matrnal Preeclampsia, HELLP syndrome or severe uteroplacental insuffuciency.- DIC due to infection or asphyxia.- Inherited marrow failure syndromes : Fanconi anemia & congenital amegakaryocytic thrombocytopenia
C. Vascular origin:- Pulmonary haemorrhage- A-V malformations- CNS haemorrhage- Hemangiomas.
Diagnostic workupA.History- Family h/o bleeding disorders- Maternal medications- Pregnancy & birth history- Maternal h/o infant with bleeding disorder- Any medications, procedures, anomalies in infant
B. Examination:First diagnose whether the infant is Sick or Well1. Sick infant:- DIC- Bacterial/ viral infections.2. Well infant:- Vit K deficiency- Isolated C.F. deficiencies- Immune thrombocytopenia- Maternal blood in infant’s GIT.
3. Patchiae, ecchymosis, mucosal bleeding: Platelet problem4. Large bruises: DIC, C.F deficiencies, liver diseases5. Enlarged spleen : Possible congenital infections or erythroblastosis.6. Jaundice : Sepsis, liver diseases, resorption of large hematoma.
C. Laboratory tests:1. Apt test : - To rule out maternal blood in infant’s GIT - Done in otherwise well infant with only GI bleeding.2. PBS :- DIC- fragmented RBCs- Congenital macrothrombocytopenias – large platelets.
3. PT4. APTT5. D-Dimer assays: Measure fibrin degradation products in DIC & Liver diseases causing defective clearing of fibrin split products.6. Specific factor assays & Von Willebrand assay: For patients with + ve family h/o.
Laboratory findings Laboratory Studies Likely Diagnosis Other useful testsPlatelets PT APTTSICK INFANTS DIC, sepsis, hypoxia, acidosis, cold Fibrinogen, FDP, Sepsis stress screen Platelet consumption LFT, Albumin (NEC, Renal vein thrombosis, N N marrow infiltration, Sepsis) Liver disease N Compromised vascular integrity N N N (hypoxia, prematurity, acidosis)
Laboratory Studies Likely Diagnosis Other useful testsPlatelets PT APTTHEALTHY INFANTS Immune thrombocytopenia Maternal platelet count, N N Bone marrow hypoplasia Platelet antigen typing, Bone marrow, Fibrinogen, FDP, Factor VII & IX assays N Vitamin K Deficiency N N Heriditory C.F. deficiencies B.T. Bleeding d/t local factors, Platelet aggregometry N N N Plt function anomalies, Urea clot solubility Factor XIII deficiency(rare)
Treatment Of BleedingA. Inj Vitamin K1 (Aquaminophyton)- 1 mg IV or IM if not given at birth.- Infants on TPN- Infants on Antibiotics > 2 weeks: at least 0.5mg Vit K weekly.- Preferred rather than FFP for prolonged PT & PTT, FFP should be reserved for emergencies.
B. FFP:- 10ml/kg IV for active bleeding- Repeated 8-12 hrly as needed.- Replaces C.F. immediately.C. Platelets:- 1 Unit of platelet raises count by 50,000-10,000/mm3.- Platelet count slowly decreases if stores 3-5 days.
D. Fresh whole blood:- 10ml/kg- Can be repeated after 6-8 hrs as needed.E. Clotting factor concetrates- Severe VWD :- VWF containing plasma derived factor VIII concetrate.- Known deficiency of factor VIII or IX : Recombinent DNA derived factor VIII and IX concetrate
F. Disorders due to problems other than hemostatic proteins :- Rule out the underlying possibilities- eg. Infection, Liver rupture, catheter, NEC.G. T/t of specific disorders :1. DIC :- Treat the underlying cause i.e. sepsis, NEC- Make sure that Vit K1 has been given.
- Platelets/ FFP to keep platelet counts > 50,000/ml and to stop bleeding.- If bleeding persists, i. Exchange transfusion with fresh whole blood /Packed RBC/Platelets/FFP ii. Continuous transfusion with platelets, packed RBCs or FFP as needed. iii. For hypofibrinogenemia : Cryoprecipitate (10ml/kg)
2. Haemorrhagic disease of newborn- Incidance is 1:200 neonates (Not given Vit-K).- For active bleeding : 10ml/kg FFP & Inj Vitamin K 1mg IV .- If mother is on t/t with Phenytoin, primidone, Methoximide or Phenobarbital, the infant may be deficient in vit K .Inj Vit K 10mg IM 24 hours before delivery . Newborn is monitored for signs of bleeding, PT, APTT.
3. Delayed Hemorrhagic disease of newborn:- Occurs at 4-12 weeks of age- Not very common in infants who received Vit K at birth.- Exclusively breast feeding infant- Infant on t/t with broad spectrum antibiotics- Infant with malabsorption T/t: Vitamin K1- 1mg/week orally for first 3 months of life.
Referances*. Sutor AH, von Kries R, Marlies Conelissen EA, Mcninch, Andrew M. VitaminK Deficiency Bleeding (VKDB) in infancy.Thrombosis and Haemostasis 1999;81: 456-461.* Narang A. Hemorrhagic Disease of Newborn. Indian Pediatr 1989, 26:523-524. 4. von Kries R, Hanawa Y. Neonatal vitamin K prophylaxis.Thrombosis and Haemostasis 1993, 69:293-295.