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WELCOME TO ALL

Coagulopathy in childrenDr. Mohammed Saiful IslamResident ( Phase:A),Department of Paediatric Surgery, BSMMU.Bangladesh.

20/09/2016, Venue: Paediatric surgery class room.2

ObjectivesTo define & understand the extent of coagulopathy.A review of coagulation pathways.Discussions on Platelet disorders.Key points discussions associated with coagulation factor disorders.Perioperative strategies to meet the challenges of coagulopathy in case of children.

Definition:Group of medical conditions resulting from deficiency of clotting factors, inhibition of coagulation process or excessive activity of the fibrinolytic system.

Reff: de Gruchy 5th

Extent of Coagulopaty:

VESSEL WALL ABNORMALITIES:

PLATELETS DISORDER:

COAGULATION DISORDER:

INTRINSIC EXTRINSICPROTHROMBIN(II) THROMBIN(III)

FIBRINOGENFIBRIN

(I)VX

Tissue ThromboplastinCollagenXIIXIIXVIII

VIIPTPTTVit.K, LiverCLOTTING MECHANISM (Easy to keep in mind)

PLATELETS DISORDERS:

QUANTITATIVE PLATELETS DISORDERs.

QUALITATIVE PLATELET DYSFUNCTION.

QUANTITATIVE PLATELETS DISORDER (Thrombocytopenia)

Mechanisms:1. Failure of megakaryocytic maturation.2. Excessive platelets consumption after their release into circulation i.e ITP, DIC etc.3. Platelets sequestration in enlarged spleen i.e HYPERSPLEENISM.

QUANTITATIVE PLATELETS DISORDER (Continued)S/S:Petechial cutaneous bleeding,Intracranial bleeding,Oozing from mucus membrane & skin surface.Lab: Decreased platelets count and prolong bleeding time.

(Thrombocytopenia) Causes:

Marrow Disorder Aplastic anemia.Haematological malignancy.Myelodysplastic disorder.B12 defficiency.

Non Marrow Disorder Immune disorders. ITP, Drug induced. Sec: ALL, SLE. Post transfusion. DIC. Human immunodeficiency syndrome. Hyperspleenism. Haemangiomas. Sepsis. Viral infection.

Thrombocytopenia (Continued)Management: Rx Underlying cause. Platelet transfusion.

IDIOPATHIC THROMBOCYTOPENIC PURPURA(ITP)

An autoimmune antibody IgG is formed against unknown antigen of platelets membrane/surface.Antipletelet antibody binds to complement, but platelets are not destroyed by direct lysis.Destruction takes place in spleen, where spleenic macrophages destroyes antibody coated platelets.

IDIOPATHIC THROMBOCYTOPENIC PURPURA. (Continued) Clinical Features: Often precipitated by viral infection and usually self limiting. Asymptomatic, not febrile. Present with mucosal/skin bleeding, mennorrhagia, purpura, petechiae. Females are more affected (2:1 male/female ratio).

IDIOPATHIC THROMBOCYTOPENIC PURPURA. (Continued) LAB:Platelets below 10,000 /ml.Bone marrow will appear normal.RxPREDNISONONE: 1-2 mg/kg/day. Immunoglobulin: 1g/kg/day 2-3 days.DANAZOLE: 600mg/day response rate is 50%IMMUNOSUPPERESSIVE DRUGS: i-e vincristine, vinblastine, azathioprine, cyclosporin, cyclophosphomide. SPLEENECTOMY.Prognosis:Good, if disease is initially controlled with prednisolone, Spleenectomy is definite Rx.

QUALITATIVE PLATELET DISORDER

CONGENITAL: Glanzmanns thrombasthenia.Bernard souliar syndrome.Von Willibrands disease.

ACQUIRED Myeloproliferative disorder. Uremia. Drugs i-e NSAIDS Aspirin. Autoantibody. Fibrin degradation products.

QUALITATIVE PLATELET DISORDERGLANZMANNs THROMBASTHENIA:

Autosomal recessive disorder.Lack of receptors (glycoprotein Ib & IIIa) for fibrinogen on platelets.Platelets fails to aggregate in respons to ADP, collagen, thrombin.Clinical Features: Mucosal bleedingLAB:Platelets nos and morphology are normal B.T is prolonged Rx:Platelet transfusion

QUALITATIVE PLATELET DISORDERBERNARD SOULIER SYNDROME:

Autosomal recessive intrinsic platelets disorder.Due to lack of glycoprotein (Gp1b), receptor for vonWillibrands factor.Clinical Features:Presents with mucosal bleeding and post operative oozes.LAB:Thrombocytopenia may be present, and Platelets are abnormally large in size.BT is prolonged Von Willibrands factor Normal .Rx:Platelet transfusion

QUALITATIVE PLATELET DISORDERVON-WILLIBRANDS DISEASE:Autosomal dominant (gene for vWF is located on chromosome 12.)vWF is synthesized by endothelial cells and megakaryocytes. It acts as carrier protein for factor VIII by non-covalent bond.A defect therefore leads to decreased plasma factor VIII level.

VON-WILLIBRANDS DISEASE (Continued.)It also forms bridges between platelets and sub endothelium.There fore defect of vWF leads to prolonged bleeding.

VON-WILLIBRANDS DISEASE (Continued.)Figure: Structure and function of factor VIII-von Willebrand factor (vWF) complex.

VON-WILLIBRANDS DISEASE (Continued.)Clinical Features:Mucosal bleeding (mild-massive)LAB:Reduced level of vWF.Secondary reduction in factor VIII. Prolonged bleeding time (B.T).

VON-WILLIBRANDS DISEASE (Continued.)Rx:MILD HAEMORRHAGES:Desmopressin 0.3 g/kg, after which vWF levels usually raise 3 units in 30-90 minutes. MASSIVE HAEMORRHAGES:Factor VIII transfusion.

COAGULATION DISORDER: Coagulation factor disorder can be either due to single factor def., i.e. a congenital deficiency, e.g factor VIII resulting in HAEMOPHILIA-A or due to multiple factor defficiency which is an acquired condition e.g Sec: to liver disease or warfarin therapy.

HEAMOPHILIA A (CLASSIC / TRUE HAEMOPHILIA) HAEMOPHILLIA B (CHRISTMAS DISEASE).Other specific factor deficiency (e.g. Factor , , etc. deficiency).

COAGULATION DISORDER:CONGENITAL BLEEDING DISORDER:

COAGULATION DISORDERACQUIRED BLEEDING DISORDER

DICLiver disease Renal diseaseVitamin K deficiencyMassive blood transfusionAnticoagulant drugs.

HAEMOPHILIAX-linked recessive disorder. Due to deficiency of factor VIII (Haemophiia A) or factor IX (Haemophiia B) .

HAEAMOPHILIA (Continued.)

C/F:Bleeding occurs as bruising at the age of 6 months.Trauma results in excessively bleeding.Recurrent bleeding /hemorrhage in knee, elbow, ankle, and hip. (Hemarthrosis).Mucus membrane /internal bleeding of mouth, lips, gums, brain and kidney also occur.Muscle haematoma esp. calf and Psoas muscle .RxCryoprecipitate or Factor VIII infusion ( in Haemophiia A) & Factor IX infusion (in Haemophilia B)

HAEAMOPHILIA (Continued.)LONG TERM COMPLICATIONsCOMPLICATION due to repeated hemorrhage:Arthropathy of large joints eg knee, elbowMuscle atrophy due to haematomaMononeuropathy due to pressure of haematoma.COMPLICATION due to therapyAntifactor VIII antibody develops.Virus transmission Hepatitis B,C + HIV etc.

HAEAMOPHILIA (Continued.)Figure: Haemarthrosis & Arthropathy.

SURGERY IN A CHILD WITH HAEMOPHILLIA:In minor Surgery:Factor VIII should be at least 50% of the normal predicted value. In Major Surgery: Factor VIII should be 100%. Half life of Factor VIII is 8 to 12 hours.Factor VIII should be substituted just before surgery & 12 hours after the initial dose ( Target is to pass the time of reactionary haemorrhage).

Calculation of Factor V

% Desired Wt in KgAmount of Factor V = KHere, value of K is 1.5 for Haemophilia A & 0.75 for Haemophilia B.

DISSAMINATED INTRAVASCULAR COAGULATION

Disseminated Intravascular Coagulation (DIC) is a thrombo-haemorrhagic disorder appearing as a secondary complication of several diseases, where there is consumption of platelets and clotting factors in the circulation as well as secondary activation of plasminogen fibrinolytic system.

DIC:CAUSES

A Infection: 1. Gram negative septicaemia 2. Meningococcaemia3. Pneumococcaemia4.Malaria B. Massive injury: 1. Massive trauma 2. Extensive burn (severe burn) 3. Extensive surgery (brain, lung, prostate, etc.) C. Carcinoma: 1. Pancreas 2. Lungs 3. Stomach 4. Prostate, etc.

D. Others: 1. Transfusion reaction 2. Fat embolism 3. Snake bite 4. Shock, etc.

Fig: Pathophysiology of disseminated intravascular coagulation.

DIC (Continued.)CLINICAL FEATURES:Bleeding & thrombosis, bleeding is more than thrombosis.Features of complications.LAB:ThrombocytopeniaProlong PTAPTT may be normal/increasedLow fibrinogenIncreased level FDP/D-dimmer

Treatment of DICRx. Underlying cause.General Measures: Correction & prevention of :DehydrationRenal failureAcidosis and ShockReplacement:Platelets transfusion if platelets counts below 10,000/mlCryoprecipitate to maintain plasma fibrinogen level above 150 mg/dl FFPHeparin, if there is DVT, Pulmonary thrombosis.

WARCRAFT FOR SURGERY IN A CHILD HAVING ANTICOAGULANT THERAPYIf patient on oral anticoaguant:Dose adjustment for INR within 2.5 to 3.5.During surgery INR should be 1.5 or less. If patient on Parenteral anticoaguant:Per operative APTT should be within 1.5 to 2.5 times of normal range.

WARCRAFT FOR SURGERY (Continued.)During emergency surgery:Inj. Vitamin K should be administered.FFP & Factor concentrate of , V, X & X should be kept in hand.Per operative & Post operative monitoring of PT, INR.

WARCRAFT FOR SURGERY (Continued.)During elective surgery:Minor surgery:Oral anticoagulant should be stopped 2 to 3 days prior to surgery.Major surgery:Oral anticoagulant should be stopped 4 to 5 days prior to surgery.Then low molecular weight heparin should be started.Heparin should be stopped 4 hours prior to surgery & restarted 12 hours after surgery.

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