DOUBLE THE HIT(T) TWICE THE FONDA

Transcription

1 DOUBLE THE HIT(T) TWICE THE FONDA KIRSTY SHARPLIN HAEMATOLOGY REGISTRAR ROYAL ADELAIDE HOSPITAL

2 PATIENT AB: 50 year old female presented ED w Chest pain at 0500 PMHx: Depression Social: Non smoker, occasional alcohol Medication: Seroquel, COCP, Quetiapine melatonin zolpiderm NKDA Inv: Chest X-ray: sub segmental consolidation Imp: Pneumonia

3 BUT WHY IS THIS BEING PRESENTED AT HAEMATOLOGY CONFERENCE Represented to ED 3 weeks later Awoke with leg pain, worsening shortness of breath CTPA 31/3/16 demonstrated extensive bilateral pulmonary emboli Ultrasound confirmed thrombus in the left external iliac and common femoral veins. CBE - Platelet 237, Hb 127, WCC 10.8 Normal Renal Function and Coags

4 MANAGEMENT Anticoagulated Apixaban then enoxaparin ECHO: Normal pulmonary artery pressure and mild Tricuspid Regurgitation Developed PR bleeding Changed IV heparin Stable for 24 hours, recommenced therapeutic enoxaparin ongoing workup as essentially unprovoked PE Discharged home after 7 days of treatment dose enoxaparin with Apixaban

5 HOWEVER Represented 4 days later with worsening leg pain and increased swelling Ultrasound demonstrated extension of occlusive thrombus in left leg

6 DDX; Non compliance Apixaban failure Antiphospholipid antibody syndrome Malignancy

7 THAT PLT COUNT HIT THE SPOT! Full blood count this admission platelet count of 63 x 10 9 /L baseline of 237 x 10 9 /L. 4-T score was high (7)

8 PATHOPHYSIOLOGY PF4 + heparin Formation polyclonal IgG Early isotype switch Release more PF4 Binds FCƳIIa on Plt Activates platelets Thrombin generation and thrombosis

9 DIAGNOSTIC TECHNIQUES First and foremost HIT remains a combined clinical and laboratory diagnosis 4 T score (how do you spell that.)

10 LOW RISK 4T SCORE CAN RULE OUT HEPARIN-INDUCED THROMBOCYTOPENIA Prapti, A et.al, Blood 2009

11 LABORATORY METHODS IN HIT Immunoassays: ELISA PAgiA Lateral Flow Assay Automated LIA Automated chromogenic Functional assays: Platelet aggregometry (HIPA) Serotonin release assay LTA WBA Flow Favaloro et.al 2017

12 ACUSTAR- HIT-IGG (PF4 HEPARIN) IMMUNOASSAY Detect binding of anti heparin-pf4 antibodies Mono or polyspecific High NPV The higher the result the higher the PPV

13 STRONG POSITIVE (>4.0) Pt AB had strongly +ve HIT ab Heparin induced platelet aggregation Serotonin release assay confirmed HIT

14

15 HIT A WALL. Commenced Argatroban aptt of times baseline. Despite this No platelet recovery was achieved. After 10 days of Argatroban she developed a right leg DVT Fondaparinux was commenced aiming for a trough level of anti Xa- activity close to 1.0 ug/ml. After 13 days of treatment there was still no significant platelet recovery Concern re fondaparinux antibodies

16 FONDAPARINUX

17 REFRACTORY HEPARIN-INDUCED THROMBOCYTOPENIA WITH THROMBOSIS (HITT) The expected recovery on withdrawal heparin 4-10 days Ongoing refractory thrombocytopaenia despite cessation of heparin Often associated with ongoing thrombotic complications More severe platelet nadir In our case Extensive PE and lower limb DVT with bleeding requiring Heparin Development of HIT as confirmed with high 4T, +ve Acustar, +HIPA and SRA Lack of improvement on cessation of heparin Ongoing thrombotic complications Plt nadir 44

18 IVIG TIME TO HIT T THE ROAD International consultation recommended IVIG at dose of 2mg/kg over 2 days Why controversy over IVIG in thrombotic condition?

19 PLATELET COUNT TRACKED WITH ANTICOAGULANT Dr J. von Wielligh

20 Padmanabhan et al, Chest 2017

21 THE EVIDENCE Worldwide 13 cases (now 14) of refractory HIT which have responded to IVIG Mechanism of IVIgG binds to the Fc receptor on platelets downregulates platelet activation by HIT antibodies. In order for the effect to be realised, high doses of IVIG required Warning gratuitous detail follows. Polymorphisms in the plt receptor FcgRIIa (RR131 or HR131) may be relatively resistant to IVIg treatment May also in part explain differing degrees of severity of HIT

22 OUTCOME Thankfully no major post thrombotic syndrome So can walk off into the sunset of Tatooine Remains on Rivoroxaban Now has negative HIPA and Accustar

23 QUESTIONS (Will I pass?) Is it possible to ever have heparin again? Does the COCP on its own explain the event in the first place given the extent of thrombus?

24 ACKNOWLEDGMENTS Kobie Von Wielligh for graphics slides Simon Mcrae snappy title and his patience in handling a barage of stressed phone calls about this case Olivia Yacoub and Elizabeth Duncan teaching me everything haemostasis with patience and understanding

25 REFERENCES: Favalora E, McCaughn G, Pasalic L. Clinical and laboratory diagnosis of heparin induced thrombocytopenia: an update Pathology (4) Greinacher A. Heparin-induced thrombocytopenia. N Engl J Med. 2015;373: Khandelwal S & Arepally GM Immune pathogenesis of heparin-induced thrombocytopenia. Thromb Haemost Oct 28;116(5): Epub 2016 Jul 28 McKenzie DS & Anufiri J. Successful use of Intravenous Immunoglobulin G to Treat Refractory Heparin-Induced Thrombocytopaenia with Nagler M & Cuker A Profile of Instrumentation Laboratory s HemosIL AcuStar HIT-Ab(PF4-H) assay for diagnosis of heparin-induced thrombocytopenia Padmanabhan A, Jones CG, Shannon, M. Pechauer M, Brian R. Curtis BR, Bougie DWMS, Irani, Byant BJ, Alperin JB, Deloughery TG, Mulvey KP, Dhakal B, Wen, R, Demin Wang & Aster RH. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia 2017 Chest Prapti, Ap, Burke C, Matevoysyan K, Frenkel EP, Sarode R & ShnYM. Low Risk 4T Score Can Rule out Heparin-Induced Thrombocytopenia Blood Vianello F, Smbado L, Scarparo P, Lombardi A, Bernadi D, Plebani M & Fabrs F. Comparison of three different immunoassays in the diagnosis of heparin-induced thrombocytopenia. JournalExpert Review of Molecular Diagnostics 17(5), 2017