De presentatie wordt gedownload. Even geduld aub

De presentatie wordt gedownload. Even geduld aub

laboratoriumdiagnostiek bij heparine geinduceerde trombopenie

Verwante presentaties


Presentatie over: "laboratoriumdiagnostiek bij heparine geinduceerde trombopenie"— Transcript van de presentatie:

1 laboratoriumdiagnostiek bij heparine geinduceerde trombopenie
Nascholingsbijeenkomst NVKC Regio-Oost De Lutte 12 januari 2007 Henk Adriaansen KCHL, Gelre Ziekenhuizen Apeldoorn-Zutphen

2 Etiology of Thrombocytopenia
Decreased production Infection, chemo, alcohol, B12/folate, MDS, leukemia Increased destruction DIC, TTP, PTP, drugs, infection, HELLP, cardiopulmonary bypass Dilutional or distributional Excessive pRBC transfused, splenomegaly, pseudothrombocytopenia

3 Pseudothrombocytopenia
About 0.3% of population Caused by EDTA Benign, lab only phenomena, may be intermittant Platelet clumps on smear Re-run CBC in citrate or heparin

4 Drugs List grows longer every day Most common: Heparin Antibiotics
Zantac Quinine Antiplatelet drugs Antiepileptics Antiarrythmics

5 Thrombocytopenia due to drugs
Heparin is a whole separate issue Stop the drug & wait for recovery Improvement usually in few days-week No effective growth factors to date IL-11 (Neumega) approved for chemotherapy related thrombocytopenia Doesn’t work

6 Heparin Induced Thrombocytopenia (HIT)
Seen in up to 10% of patients on heparin Most are non-immune More common with UFH than LMWH Up to 5% with UFH 1% with LMWH Can be seen with heparin flushes, heparin coated catheters, heparin during dialysis

7 HIT Type 1 Non-immune response to heparin
Usually mild drop in platelets (>100,000) 1-2 days after start of heparin Often returns to normal on heparin Usually no clinical consequence Usually responds to simple cessation of heparin Direct effect of heparin on platelet activation

8 HIT Type 2 Immune mediated
Antibody against heparin-platelet factor 4 complex Antibody binds to Fc receptor & activates platelet Potentially life/limb threatening condition Leads to thrombocytopenia, arterial and venous thromboses Antibodies against the heparin-platelet factor 4 complex

9

10 Tests for HIT Diagnosis is clinical
Do not wait for tests to start therapy- both are send outs and take days Serotonin release assay – Functional assay that looks for platelet activation ELISA for PF 4 Antigen assay for heparin/PF4 complex Platelet aggregation Geltest Diamed

11 Functionele testen voor HIT
bloedplaatjesaggregatie test (PAT) 14C-serotonine release test (14C-SRA) ATP release test (lumi-aggregometry) heparine geinduceerde bloedplaatjesactivatie test (HIPA) flow cytometrische bepaling van bloedplaatjes micropartikels flowcytometrische bepaling van annexine-V binding

12 14C-serotonine release test (14C-SRA) = gouden standaard
PRP+14C-serotonine: 15’ op 37°C + test serum + heparine(1): 60’ op 22°C +0.5% EDTA centrifugatie scintillatieteller

13 Serotonin Release Assay
Measures the release of serotonin from aggregated platelets in serum of patient with HIT; relies on platelet aggregation in the presence of heparin Advantages High specificity and sensitivity Validated in blinded assessment of a clinical trial Disadvantages Technically demanding and time-consuming Requires the use of radioactive materials Not widely available

14

15 ELISA Immunologische bepaling van HIT antilichamen
ELISA test voor heparine-PF4 antistoffen microtiterplaat gecoat met hep-PF4 +patientenserum of positieve controle of negatieve controle, 60’ op KT 5x wassen + antihumaan IgG,A,Mperoxidase conjugaat, 60’ op KT+ 5x wassen ortho-phenyleen diameer/ureumperoxidase substraat,5’ op KT

16 Tests for HIT Serotonin Release Assay ELISA for heparin-PF4 complex
Sensitivity 88% 97% Specificity 100% 86% Positive Predictive Value 93% Negative Predictive Value 81% 95%

17

18 Platelet Aggregation Assay
Measures platelet aggregation of IgG in serum or plasma of a HIT patient treated with heparin Donor platelets can be washed or suspended in citrated plasma Advantages Easily performed in most laboratories Specificity greater than 90% Disadvantages Low sensitivity: 35%–81%; sensitivity higher using washed platelets Reactivity varies among donor platelets

19 Ter discussie het Diamed Gelsysteem voor het aantonen van HIT

20 HIT Type 2 Thrombotic Sequelae of HIT:
Venous: arterial thrombosis = 4:1 DVT (50%) PE (25%) Acute limb ischemia (10-20%) Warfarin-associated venous limb gangrene (5-10%) Acute thrombotic stroke or MI (3-5%)

21 HIT Type 2 50% risk of thrombosis over 30 days with cessation of heparin alone Thrombotic tendency exists for at least 40 days after stopping heparin Overall risk of thrombotic complication: 38-76%

22 HIT Type 2 Time course Typically occurs 4-14 days after starting heparin Has occurred as soon as 10 hours after re-exposure to heparin Has occurred 3-4 days after cessation of heparin Onset after 2 weeks is unusual

23 HIT Diagnosis Consider in anyone with unexplained drop in platelets to < 150,000 or 50% decrease while on heparin Diagnosis is clinical Do not wait for lab test results to start treatment

24 Pathofysiologie HIT Verschillende componenten betrokken bij het ontstaansmechanisme van HIT: Trombocyten HIT-antistoffen FcγRII alfa isovormen Endotheliale cellen Leukocyten Inflammatoire toestand J. Walenga et al., Sem. Throm. Hem., 2004 T. Warkentin, Hematology, 2003 Newman and Chong, Blood, 2000

25 Pathofysiologie HIT-antistoffen en bloedplaatjes
Binding van heparine aan PF4 tetrameer  neoepitope (IL8, NAP2 = CXC chemokines) Vorming van AL tegen heparine-PF4 complex (IgG1 > IgG3 > IgG2 > IgG4 >> IgA en IgM) Fab-regio van het AL bindt heparine-PF4 complex, terwijl het Fc-gedeelte FcγRII op de Blp-membraan bindt Activatie van de trombocyten met secretie van meer PF4, stollingsfactoren,... uit de alfa-granules secretie van serotonine, ADP, Ca2+ uit de dense bodies => Amplificatie Vorming van trombocytenaggregaten

26 Pathofysiologie Receptor isovormen 2 isovormen op aminozuurplaats 131:
een arginine (R) of een histidine (H) FcγRII-H bindt IgG2 met hogere affiniteit dan de FcγRII-R  hogere frekwentie HIT bij patienten met H/H genotype (Brandt et al., Denomme et al.)


Download ppt "laboratoriumdiagnostiek bij heparine geinduceerde trombopenie"

Verwante presentaties


Ads door Google