approach_to_bleeding[1].pptx in a neonate

Approach to bleeding

1. Moderator :Dr. Girish Presentor :Dr. Amruta Dr. Nida Approach to bleeding neonate

2. Introduction Neonatal bleeding may present a diagnostic challenge to the caregiver. Excess or deficiencies of certain coagulation/anticoagulation proteins coupled with multiple acquired or prothrombotic risk factors or thrombocytopenia can result in a hemorrhagic manifestations in the neonatal period.

3. Hemostasis refers to the process in which bleeding is controlled at the site of damaged endothelium. The process of hemostasis involves the interaction between endothelium, subendothelium , platelets, circulating cells, and plasma proteins. Blood vessel injury leads to an immediate, local response of both plasma and cellular components. Thrombosis is confined to the area of injury, leading to eventual tissue repair. The result is a localized, firm thrombosis, leading to cessation of bleeding. Hemostasis

4. The intact vascular endothelium is the primary barrier against hemorrhage. The endothelial cells that line the vessel wall normally inhibit coagulation and provide a smooth surface that permits rapid blood flow. After vascular injury, vasoconstriction occurs and flowing blood comes in contact with the subendothelial matrix. Von Willebrand factor (VWF) changes conformation and provides the glue to whichthe platelet VWF receptor, the glycoprotein Ib complex, binds, tethering platelets to sites of injury.

5. Complex signaling occurs from the outside membrane receptor to intracellular pathways, activating the platelets and triggering secretion of storage granules containing adenosine diphosphate (ADP), serotonin, and stored plasma and platelet membrane proteins. On activation, the platelet receptor fo r fibrinogen, αIIbβ3 , is switched on (“inside out” signaling) to bind fibrinogen and triggers the aggregation and recruitment of other platelets to form the platelet plug. One of the subendothelial matrix proteins that is exposed after vascular injury is tissue factor . Exposed tissue factor binds to factor VII and activates the clotting cascade. The activated clotting factor then initiates the activation of the next sequential clotting factor in a systematic manner

6. Injury to endothelial lining Vasoconstriction Platelet plug formation Coagulation Clot retraction and repair Fibrinolysis

7. The Neonatal Hemostatic System – HOW IS IT DIFFERENT A t birth ,concentrations of vitamin k dependent (2,7,9,10) and factor 11 and 13 are reduced to about 50% of adult value and are further reduced in preterms Concentrations of naturally occurring anticoagulants, antithrombin protein c and protein s are low at birth and as a result both thrombin generation and thrombin inhibition is reduced in newborn period . Plasminogen is also low in neonatal period resulting in a relatively hypofibrinolytic state .

8. Clinical approach to the bleeding neonate: 1. Was the baby sick or well at the onset of bleeding?

2. Was Vit K given to the baby?

3. Is the bleeding generalized or localized?

4. Is there a family history of bleeding/ coagulation defects?

5. Is there a h/o maternal thrombocytopenia, connective tissue disease, PIH or intake of barbiturates, phenytoin, aspirin, rifampin , INH or warfarin?

9. 6. What was the age of onset of bleeding
7. Is the bleeding petechial with small mucosal hemorrhages or are the bleeds large?
8. Are the coexisting signs like conjugated hyperbilirubinemia , organomegaly , signs of sepsis?

10. Presentations in newborn are unique
EXCESSIVE BLEEDING can appear as • Expanded cephalhematoma .
• Prolonged bleeding after circumcision.
• Oozing from venipuncture site and line placement site.
• Bleeding from umbilicus Sick neonate may present as
Bleed from bladder – hematuria Mucous membrane bleed
IC bleed • Pulmonary hemorrhage

11. On Examination
Sick infant-DIC, sepsis, liver diseases Well infant –Vit K deficiency, Clotting factor deficiency.
Petechiae, small ecchymosis –platelet disease
Deep bruises-clotting factors deficiency, DIC, liver disorders, or vit k deficiency
Splenomegaly congenital Infection/erythroblastosis.
Jaundice – TORCH infections or LIVER disease
Abnormal retinal finding- TORCH infection

12. Bleeding before birth 1. In ut e ro a) Feto maternal hemorr h age b) Twin to twin transfusion syndrome 2. Placental bleeding a)Abruptio placenta b)Placenta previa

13. Bleeding after birth Platelets number Decrease in number of platelets: Congenital infections and certain syndromes Increase in destruction or consumption Infection NEC Asphyxia Maternal ITP - Throbocytopenia in a neonate can be a presenting sign of ITP or SLE in an asymptomatic mother HELP/ Preecamplsia DIC Hemangioma

14. NAIT (NEONATAL ALLOIMMUNE THROMBOCYTOPENIA) Antibody is produced in the mother against specific human platelet antigen present in fetus but absent in mother The antigen is inherited from father It is the most common cause of early onset severe thrombocytopenia (less than 50 thousand on first day of life) Investigations: Antigen screening for HPA1, HPA 3, HPA 15 Resolves within 2 weeks Management : Platelet transfusion and IVIG

15. Platelet function defect Bernard soulier syndrome Glanzmann’s Thrombasthenia

16. Disseminated Intravascular Coagulation DIC is a clinicopathologic syndrome resulting into widespread intravascular coagulation induced by procoagulants that are introduced into or produced in the blood circulation and overcome the natural anticoagulant mechanisms. Baby appears sick and may have petechiae GI hemorrhage, oozing from venipunctures, infection, asphyxia, Platelet count is decreased, and PT and APTT are increased . Fragmented RBCs' are seen on PS. Fibrinogen decreased and D-dimers are increased . Spectrum of DIC includes: • Thrombosis, progressive organ dysfunction, bleeding and the end result is usually hemorrhage

17. Management of DIC • DIC is a secondary phenomenon, management is reversal of the underlying disease process. • Supportive therapy with FFP, cryoprecipitate and platelets is done to maintain adequate hemostasis. • The platelet count should be maintained above 50000/mm3. • FFP (10-15 mL/kg) can be used to replace hemostatic proteins • Cryoprecipitate (5-10 ml/kg) is a better source of fibrinogen, which should be maintained above 1 g /L

18. Coagulation defect Inherited Haemophilia A and B Von willebrand disease Factor 7,10,12 deficiency Afibrinogenesis Acquired Vitamin K deficiency/Hemorrhagic disease of newborn DIC Warfarin overdose

19. Hemorrhagic Disease of the Newborn RISK FACTORS: Moderate transient deficiencies of vitamin K dependent factors ,r educed body store of Vit K of the newborn due to lack of free vitamin K in the mother (more common among the preterm infants). • No vitamin K administration after birth. (Breast milk is a poor source of vitamin K) more common in breast-fed infants than formula-fed ones. Liver immaturity or disease. • Malabsorpation disease (biliary atresia, cystic fibrosis, hepatitis). • Absence of bacterial intestinal flora (that form vitamin K): Total parenteral alimentation, Broad spectrum antibiotics. • Maternal medication: phenytoin, phenobarbital, salicylates, rifampcin and isoniazid

20. Types Early : within 24 hrs , mucosal and GI bleed are main manifestations At risk mothers should be given about 10 to 20 mg/day of vitamin K orally for 15 to 30 days before delivery. • When Warfarin is to be prescribed it is advised that it is avoided between wks 6 &12 of gestation (Teratogenic) and close to term (neonatal bleeding.) Vitamin k inj 1mg kg IM to be given and repeat the same dose after 24 hrs Classical : 1-7 days , GI bleed and ICH IV or SC VITAMIN K 1mg Late : 2-12 weeks , ICH RISK FACTORS :Breast feeding , Prolonged antibiotic therapy or Malabsorption Treatment : Vitamin k 1mg per week for 1 st 3months may prevent late HDN

21. VITAMIN K PROPHYLAXIS Newborn should receive 0.5 – 1mg Vitamin K1 intramuscularly at birth But administration of high doses of Vitamin K3 (Menadione sodium bisulphate ) which is available as 10mg/ml can lead to severe hemolysis and jaundice and even kernicterus.

22. Hemophilia The most common congenital bleeding disorders are hemophilia A (FVIII deficiency) and hemophilia B (factor IX deficiency), both being inherited as X-linked recessive. The incidence of hemophilia A is 1 per 5000 males and for hemophilia B is 1 per 20,000 males. Approximately one-third of cases will occur in the absence of a positive family history. • They account for 90-95% of severe congenital coagulation deficiencies. • Affect all racial group

23. Treatment for bleeding episodes is replacement of the specific factor and should be done as quickly as possible and in consultation with pediatric hematology, as there are a number of factor concentrates that are commercially available for both FVIII and factor IX deficiency Adjuvant therapies for hemophilia, such as desmopressin, may increase factors to hemostatic levels, and can be useful for management of minor bleeding or procedures in patients with mild factor VIII deficiency. Fresh frozen plasma (FFP) should only be used in the instance of acute hemorrhage when confirmatory testing is not yet availabl e

24. von Willebrand Disease The primary plasma protein required for platelet adhesion, vWF , also has a role in platelet aggregation and serves as the carrier for FVIII. Absence, reduction, or abnormal function of vWF results in defects in platelet adhesion and aggregation, increasing one’s risk for bleeding Neonates have higher plasma concentrations of vWF and an increased proportion of high-molecular-weight vWF multimers than older children or adults. As a result, presentation of von Willebrand disease ( vWD ) during the neonatal period is rare.

25. Coagulation testing may demonstrate an isolated prolonged APTT and prolongation of epinephrine and ADP closure times as measured by the PFA100. Further testing would evaluate the levels of vWF ( vWF antigen assay), platelet-binding function ( ristocetin cofactor assay), and FVIII-binding function (FVIII activity). M anagement of type 3 V WD should consist of factor replacement using an intermediate purity FVIII concentrate containing the high-molecular-weight multimers of V WF. Desmopressin should be reserved for those patients with type 1 V WD but, as noted above, should only be used after consultation with a pediatric hematologist, as it carries a risk of symptomatic hyponatremia in infants.

26. Case scenario Here is a B/O Shabana born to primi mother at 40 wks of GA with MSL Mother k/c/o psychosis on Tab olanzapine At 45hrs of life presented with hemetemesis and dark stools and per vaginal bleed Mother's platelet 1.4L USG abdomen and erect x ray Normal CBC hb 20.2. Plt -92k (repeat normal) PT/APTT/INR - 18.8/68.7/1.36 Peripheral smea r - Macrocytic and normocytic with many polychromatophilic erythrocytes Vit K, Platelet and FFP given

27. No h/o of umbilical cord bleeding No h/o of refusal of feed, vomiting, lethargy or abdominal distension No h/o pallor ,yellow discolouration of skin No h/o bleed from injection site Pediatric hematologist opinion was taken and Factor 9 ,11 deficiency was suspected

28. Case scenario Here is a B/O Amreen born to primi at 37WOG via vaginal delivery , at 19 hrs of life baby presented with fresh bleed from oral cavity since 10 minutes Baby was feeding well,had passed urine and passed meconium No h/o of bleeding from urine/stool No h/o of umbilical cord bleeding No h/o of refusal of feed, vomiting, lethargy or abdominal distension No h/o drug intake in mother No h/o pallor ,yellow discolouration of skin No h/o bleed from injection site No h/o vaginal bleed

29. On arrival baby was bleeding from oral cavity ( no oral cavity lesion) approximately 10 to 20ml of blood with altered aspirate from GI Tract was also present. Baby kept NPO IV Line secured routine investigation sent Initial sepsis screen was negative with INR WNL usg abd and pelvis , erect X-ray abd was normal peds surgery opinion taken adviced to keep NPO inj rantac od for 3days 2 times 10ml / kg FFP transfusion done Day 3 investigation showed thrombocytopenia 35k and ANC positive so one 10ml /kg platelet transfusion done bleeding resolved .

30. Case senario 3. Here is B/O Meghana presented at 40hrsof life with staining of diaper with blood with no any other bleeding manifestation no abdominal distension Baby active feeding well Stomach wash and rectal wash given no bleed CBC sent values within normal limits. Usg abd done showed ileo colic intussusception. Baby was kept NPO and then after 48 hrs intusseception resolved

31. CASE REPORT NEONATAL INTUSSUSSCEPTION : A RARE BUT IMPORTANT CAUSE OF BLEEDING PER RECTUM IN NEONATE (DEPARTMENT OF PEDIATRIC SURGERY AND NEONATOLOGY JIPMER) A full term male child born via vaginal delivery with birth weight of 2.3kg and presented on day 6 with bleeding per rectum with mild abdominal distension but no mass palpable ,Prolonged PT was documented abd hence intial diagnosis of HDN was made , but despite correction with vitamin k and ffp bleeding per rectum continued On further evaluation abdominal x ray revealed prominent bowel loops and upper GI contrast study was done to rule out volvulus ,ultrasound was done whiuch revealed ileo colic intussusception with no lead point

32. 1.AVERY’S DISEASES OF THE NEW BORN. 2.PRACTICAL PEDIATRIC HEMATOLOGY BY ANUPAM SACHDEVA. 3. FANAROFF AND MARTIN NEONATAL-PERINATAL MEDICINE. 4.CARE OF THE NEW BORN – MEHARBAN SINGH

33. Thank you.