Ophthalmic manifestation of congenital protein C deficiency - PowerPoint Presentation

Ophthalmic manifestation of congenital protein C deficiency Dr Shahla ansary peiatric heamatologyonclogist Dr Amir hesabi Assistant pediatric hematologyoncologist

Case 1CC: purpura fulminans HX: A male neonate 8 days old was born by C/S.BW 3200 gr ,G/A :40wks,I/I, parents were cousins.He was reffered from karaj hospital with purpura fulminans to Ali asghar chidren hospital Past Hx : His mother had two abortions, but did n’t have thrombophilia or stroke hx and in her family. His father also did n’t have hx thrombophilia and in his family. Drug HX: Folic acid,iron,MV P/E: His vital signs was stable and the neonate was n’t ill. He had purpura fulminans on Lt buttock , hypogastric area and lumbar and Rt forearm. His all extremities pulses were palpable. He also had mild icter .

He was admitted ,broad spectrum antibiotics and FFP were begun for him on 2nd day of his admission. His lesions were recovered by time.He lesions were debrided on 12th day on general anastasia in OR.On 14th day he had white reflex on LT eye . Ophthalmologist had advised to his parents OS angiography after his discharged from hospital on genral Anastasia in OR.Hematologist had prescribed for him warfarin. After that he achieved to ideal INR , and he discharged on 35th day with warfarin only. The final dx OS on 90th day was PHPV. Lab data: All sepsis work up were normal and PT,PTT,INR were normal. Screening tests were normal. Protein c level index case was 8% and his father was 51% and his mother was 62% Imagings : Doppler sonography upper and lower extremities were normal. Brain sonography was normal.

Case 2CC:purpura fulminans,premturity HX: A male neonate 3days old was born by C/S(GDM,Asthma).BW2200 grs ,II/II,G/A 34 weeks,with RDS who was received surfactant in Karaj hospital and referred to Aliasghar with purpura fulminans .Past hx: his parent weren’t relative , his mother in her 3rd trimester had an ICU admission. She didn’t have hx reccurent abortion , stroke and thrombophilia.His father also didn’t have hx of thrombophilia. Drug HX : Salbuthamol,Atrovent,Theophylline G,Symbicort . P/E: His vital signs were stable and the neonate was n’t ill. There was purpura fulminans in his Lt hand and forearm . capillary filing was >3s.ROM LT upper ext. was decreased.

Imagings:Doppler sonography Lt upper ext. had thrombosis in veins and vessles .Brain sono was normalHe was admitted ,broad spectrum antibiotics and FFP were begun for him on 2nd day of his admission.His lesions were recovered by time.He had convulsion during his addmision and it was stopped by Phenobarbital. He lesions were debrided on 10th day on general anastasia in OR.On 18th day he had white reflex on LT eye. Ophthalmologist had advised to his parents OS angiography after he discharged from hospital on genral Anastasia in OR. Hematologist had prescribed for him warfarin. After that he achieved to his ideal INR , and he discharged on 38th day with warfarin only. The final dx OS on 80th day was Lt vitreous hemorrhage. Lab data: All sepsis work up were normal and PT,PTT,INR were normal. Screening tests were normal. Protein c level index case was 9% and his father was 54% and his mother was 64%.

Case3CC: purpura fulminans Hx:34 days old male infant who had admittion in Aliasghar hospital with purpura fulminans in his Rt arm and forearm . He was debrided in Karaj hospital . he was discharged by his parent’s consent from Karaj hospital. He was born by C/S ( fetal movment ),G/A 35weeks,Bwt 2500,II/II.Past hx:his parent weren’t relative , his mother had IUFD in her 1st pregnancy She didn’t have hx reccurent abortion and stroke.His father also didn’t have hx thrombophilia.Drug HX:Folic acid,iron,MV P/E: Wt 2800 grs , Hc: 35 Ht: 49.His vital signs were stable and he had no good wt bearing.He had white reflexes on both his eyes.He had purpura fulminans on Rt arm and forearm with post surgical scars.Neurologic exam were normal but ROM Rt upper ext. was reduced.

He was admitted ,broad spectrum antibiotics and FFP were begun for him on the 1st day of his admission.His lesions were recovered by time.Ophthalmologist consult had seen bilateral vitreous haemorrhage on general anastasia. Hematologist had prescribed for him warfarin after lesions were healed. He discharged from hospital on 60 th day. Lab data:All sepsis work up were normal and PT,PTT,INR were normal.Screening tests were normal.Protein c level index case was 5% and his father was 53% and his mother was 66%. Imagings : Doppler sono all exterimities were normal.Brain sono had old bilateral PVL.

protein C deficiency, a genetic(AD-AR) or acquired thrombophilic abnormalityIn homozygous-deficient patients, protein C activity is usually less than 1% (reference range, 70%-140%), resulting in thromboembolism as early as in the neonatal period Protein C levels rise slowly over the first year of life and may not reach the normal adult range until after 1 year severe acquired protein C deficiency may result in thromboses as profound as in the homozygous state Discussion In contrast to the genetic form, acquired neonatal protein C deficiency occurs particularly in ill preterm babies ( respiratory distress syndrome, necrotizing enterocolitis , and neonatal sepsis ) Prevalence in general population 1/16000-1/32000 Prevalence in VTE 0.5-4%

Ocular features : vitreous, retinal and subretinal haemorrhage, retinal venous andarterial occlusion, microphthalmos, and leucocoriasecondary to retinal detachment or persistent hyperplastic primary vitreous One or both eyes may be affected The major clinical symptoms in affected newborn infants have been purpura fulminans, vitreous hemorrhage,PHPV or PFV, Retinal artery and vein occlusion and central nervous system thrombosis,SAH,Renal vein thrombosis,pulmonary embolism,DVT. In the study by Dreyfus et al, Unilateral or bilateral blindness developed in 6 of 9 children.

Under normal conditions the endothelial cell surface anticoagulant protein thrombomodulin accelerates protein C activation by about 30,000 times. Consequently, the microvasculature is the primary site of action of the protein C pathway . Thrombosis in homozygous and compound heterozygote protein C deficiency usually begins in skin capillaries and leads to purpura fulminans, underscoring the observation that ocular microvessels constitute a typical target organ.

Earlier studies : normal pregnancy and a normal delivery appear to be typical in homozygous protein C deficiency. This supports the hypothesis that the thrombotic complications and vitreous hemorrhage do not occur until after birth in affected subjects. Later studies have suggested that thromboembolic events can occur in utero on final tremester

The 1st group says that the age of onset of the first ophthalmologic symptoms has ranged from a few hours to 2 weeks after birth, usually after an uncomplicated full-term pregnancy and deliveryThe 2 nd group says that elective caesarean section should be considered at 34–36 weeks for homozygously affected individuals so that replacement protein C therapy can be given and avoid the complications associated with the deficiency

In our study we advise that ; 1-When there is purpura fulminas at birth, exact ophthalmologist examination and early treatment should be doing before 2weeks old. 2- Therapy with FFP 10-20 cc/kg( q8h-12h) starts as soon as possible till all skin necrosis heal .then warfarin does start and after 24-48 hrs FFP will stop and warfarin is continuing life long with INR 2-3. 3- If we have got Ceprotin .we start 100-120 IU/kg loading dose and maitenance dose 60 IU/kg (q6-12h)till resolution of acute event(level pro C>50%) .After that, dosage Ceprotin will adjust to maintain level proC >25% till all clinical lesions resolve.Then warfarin does start and after that Ceprotin will stop if INR `ll be 2-3. 4- If I have prenatal diagnosis hemozygote or compound heterozygote pro C deficency . We advise elective C/S at 34-36 weeks of gestations. Because of prevention or early treatment of hazard thrombotic events in CNS and eyes.

5- because of these neonate’s skin (with hemozygous pro C defficiency) are very sensitive and duration of their admission in hospital are prolonged . we advise using central line ( Broviac catheter) on general Anastasia in OR. 6-Warfarin is discontinued from 24 hrs before OR till 2 nd day after OR