LAB UPDATE Feb. 15, 2006 Dr. Beverly Dickson. H H eparin I T I nduced T hrombocytopenia An antibody...
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Transcript of LAB UPDATE Feb. 15, 2006 Dr. Beverly Dickson. H H eparin I T I nduced T hrombocytopenia An antibody...
LAB UPDATEFeb. 15, 2006
Dr. Beverly Dickson
HHeparin
IInduced
TThrombocytopenia
An antibody mediated adverse effect of heparin that is importantbecause of its strong association with venous and arterial thrombosis.
Heparin exposure may be any preparation (LMWH) by any route(flushes), and with any dose.
HEPARIN INDUCED THROMBOCYTOPENIA
Clinicopathological Syndrome
Clinical: Thrombocytopenia with or without thrombosis
Serologic: High titer platelet activating HIT antibodies by sensitive antigen and/or activation assays
Clinical Features of HITTiming of thrombocytopenia
Typical onset: between days 5 and 10 after starting heparinRapid onset: < 1 day following resumption of heparin (usually in a patient recently exposed to heparin, who therefore has residual circulating HIT antibodies)
Severity of thrombocytopeniaPlatelet count nadir: < 20,000/µL in 10% of patients; < 150,000/µL in 85% of patients
Thrombosis is common> 50% develop new thrombosisVenous thrombosis: deep venous thrombosis > pulmonary embolism > warfarin-induced venous limb gangrene > adrenal hemorrhagic necrosis* > cerebral sinus thrombosisArterial thrombosis: limb artery thrombosis > stroke syndrome > myocardial infarction > mesenteric artery thrombosis
Absence of petechiae (even with platelets < 20,000/µL)Skin lesions at heparin injection sites
Severity ranges from erythematous plaques to skin necrosisAcute systemic reactions following intravenous bolus heparin
Acute inflammatory or cardiorespiratory signs and symptoms associated with abrupt platelet count fall
Consultative Hemostasis and Thrombosis, 2002, pg358.
Consultative Hemostasis and Thrombosis 2002, pg 359
Heparin-induced Thrombocytopenia
Quinine- or Sulfa-induced Thrombocytopenia
Frequency Approx. 1/100 Approx. 1/10,000
Onset after beginning treatment
5-14 days ≥ 7 days
Platelet count 20 - 150x109/L* < 20x109/L
Sequelae Thrombosis Bleeding
Laboratory testing using patient serum
Heparin-dependent platelet activation; Immunoassay (heparin/PF4 antigen)
Drug-dependent increase in platelet-associated IgG
*Some patients have a fall in platelet count but platelet count remains > 150x109/L
DRUG INDUCED THROMBOCYTOPENIA MECHANISMS
Simposio Internacional CLAHT PERU 2004
HIT ASSAYS
Two Major Classes
Functional activation assays (Serotonin Release Assay):
Infer presence of HIT antibodies based on heparin-dependent, platelet activating properties (washed platelets)
Antigen Assays (Heparin-PF4 ELISA):
Detect HIT antibodies based upon their reactivity with platelet factor 4 (PF4) complexed to heparin or other polyanions (ELISA)
Specificity, %
HIT Diagnostic Assay Sensitivity, % Early Platelet Fall Late Platelet Fall
Platelet SRA 90-98 * >95 80-97 ‡
Heparin-induced platelet aggregation assay
90-98 * >95 ‡ 80-97 ‡
Platelet aggregation test using citrated platelet-rich plasma
35-85 90◊ 82◊
PF4/heparin EIA >90 * >95 50-93
Combination of sensitive platelet activation and PF4-dependent antigen assay
100 * >95 80-97
”Early” refers to a fall in the platelet count that begins within the first 4 d of starting heparin; “late” refers to a fall that begins on day 5 or later. The specificity varies because late thrombocytopenia due to a reason other than HIT may nevertheless show a false-positive HIT antibody result because of subclinical HIT antibody seroconversion. *Sensitivity defined in relation to those patients in prospective studies who had a positive test result when the platelet count fell by ≥50% after ≥5 days of heparin therapy, and in whom the available clinical information (particularly, evidence for alternative explanations for thrombocytopenia and the effect of stopping or continuing heparin) supported the diagnosis of HIT. However, about 30-40% of samples (app. 2% overall) give a repeated “indeterminate” result, and the activation assay is nondiagnostic.‡ Assumes that the heparin-induced platelet aggregation assay test and SRA have similar sensitivity and specificity profiles; other platelet activation end points that may also give acceptable results using washed platelets include detection of platelet-derived micro particles by flow cytometry.◊ Assumes that a 90% specificity in early thrombocytopenia attributable to non-HIT disorders (eg, nonspecific platelet activation related to acute inflammatory proteins) declines to an 82% specificity in late thrombocytopenia that may be attributable to subclinical HIT antibody seroconversion. Clinicopathologic definition assumes that at least one sensitive test result must be positive for diagnosis of HIT; specificity of the activation assay is indicated.
Localization of thromboembolic complications associated with HIT
Type of TEC Number of TECs (%)
Arterial 126 (29.2%)
Limb artery 71 (16.4%)
Thrombotic stroke 26 (6.0%)
Aortic Thrombosis 16 (3.7%)
Myocardial infarction 10 (2.3%)
Other 3 (0.7%)
Venous 306 (70.8%)
Proximal DVT 114 (26.4%)
Pulmonary embolism 103 (23.8%)
Distal DVT 78 (18.1%)
Cerebral vein (sinus) thrombosis 7 (1.6%)
Other 4 (0.9%)
Thromb Haemost 2005:94:132-5.
Simposio Internacional CLAHT PERU 2004
Clinical Assessment: Inclusion Criteria
History of heparin exposure
Thrombocytopenia during and after heparin exposure (<150,000)
Drop in platelet count (<50%) rather than absolute thrombocytopenia
Smaller drop in platelets (especially skin necrosis)
Early-onset of thrombocytopenia with heparin re-exposure caused by circulating antibodies
Platelet count may rarely be normal when patient presents with thrombosis (delayed-onset HIT)
Thrombocytopenia recovers after heparin withdrawalMedian time to platelet count recovery after heparin withdrawal is 4 days
Platelet Monitoring for HITACCP Consensus Conference, 2004
HIT risk >0.1% - platelet count monitoringPatients recently treated with heparin starting UFH
Platelet count baseline within 24 hoursAcute systemic reaction post UFH bolus
Immediate platelet countPatients receiving therapeutic dose UFH
Every other day platelet count until day 14 or UFH stopped, whichever is first
Postoperative patients, UFH prophylaxis(HIT risk >1%)Every other day platelet count until 14 days or UFH stopped.
HIT Patient Risk Groups
1-5% risk (highest)Post-op vascular, ortho, cardiac patients receiving UFH for 1-2 weeks
0.1-1% risk (rare to infrequent HIT)Medical and obstetric patients receiving prophylactic doses of UFH
Post-op patients receiving LMWH
Post-op/critical care patients with UFH flushes
Medical patients receiving LMWH after one or several preceding doses of UFH
HIT
A negative laboratorytest for HIT antibodiesshould never be usedas the sole criterion
for restarting heparintherapy.
HIT CONCLUSIONS
Routine platelet monitoring rather than HIT Antibody studies is most useful to identify patients who are at risk for thrombosisAlthough functional and antigen assays are sensitive in detecting HIT antibodies, neither is completely specific for HIT syndromeThe diagnostic interpretation of these laboratory tests must be made in the context of clinical pretest probability of HIT
Clindamycin Disk Inductive Test for Staphylococcus spp.
“D Test”
• Routinely performed on Staphylococcus that test resistant to erythromycin but are susceptible to clindamycin
• Many MRSA that cause community acquired infections have msrA gene
D TestResistance to macrolides (e.g. erythromycin) can occur by two different mechanisms with the resulting phenotypes noted below:
Mechanism Determinant
(gene)
Erythromycin Clindamycin
Efflux msrA R S
Ribosome alteration
erm R S*
erm R R
(constitutive)
msrA=macrolide streptogramin (type B) resistance
Erm=erythromycin ribosome methylase; encodes enzymes that confer inducible (MLSBi) or constitutive (MLSBc) resistance to MLS agents via methylation of the 23S rRNA
*requires induction to demonstrate resistance
MLS=macrolide lincosamide (e.g. clindamycin) streptogramin (type B)
InducibleClindamycinResistance(erm-mediated)
Helicobacter pyloriTests at PHD
CLO-Test Rapid urease Invasive
HpSA Stool antigen test Non-invasive
Sensitivity SpecificityFDA
approved test for cure
Detects active infection
CLO 80-98% 93-100% Yes Yes
HpSA 92-97% 90-95% Yes Yes
Serology 80-95% 80-95% No No
Helicobacter pylori
AGG/AGA Graded Recommendations 2005
For patients ≤ 55 years without alarm features, the clinician may use either “test and treat” for H. pylori or acid suppression therapy. (A)
Point of Care
Blood Gas (TIS)
ACT
i calcium
creatinine
6+
PT
I-STAT
Additional POC instruments: Hemocue, Accu-Chek, Clinitek, DCA 2000 (A1c)
LimitationsMethod dependent
Technique dependent
Interferences: known and unknownDrugs
Metabolic
Other
Point of Care
Chemical Pathology
Are your hands clean enough for point-of-care electrolyte analysis?
Hugh S. Lam*, Michael H.M. Chan, Pak C. Ng*, William Wong*, Robert C.K.Cheung, Alan K.W. So*, Tai F. Fok* and Christopher W.K. Lam
Departments of *Paediatrics and Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
______________________________________________________________________
Pathology (August 2005) 37(4) pp.299-304
The patient is a 75 year old female with history of frequent TIA, recently placed on coumadin
Upon ambulatory clinic visit her I-STAT INR was > 8.0 but Core Lab INR was 4.1
What might cause this discrepancy?→ technique
→ interference
→ reagents
→ instrument malfunction
Case #1 POC/INR
Lupus anticoagulant/anticardiolipin Ab
LMWH
Direct thrombin inhibitors
Daptomycin
POC/INRInterferences
Case #2 ED/I-STAT +6
A middle aged male presented to the ED post grand mal seizure. Patient had a history of hyponatremic episodes secondary to anti-convulsant drug therapy.
I-STAT Core Lab
Na 132 140
K 3.7 4.0
Cl 103 100
BUN 13 10
AG N/A 31
Glu 159 158
Hgb 17 14
A whole blood glucose test strip that delivers plasma-like test results.
Accu-Chek Inform MeterAccu-Chek Comfort Curve Strip
Case #3 ICU/Accu-Chek Inform Meter
The patient is a 75 year old male who was transferred from Lake Pointe in septic shock s/p hernia repair. The patient developed renal failure, liver failure with coagulopathy and respiratory failure. Multiple POC glucoses performed, multiple results discrepant with laboratory.
Date Time* Core Lab
Accu-Chek
Jan 9 0754 109 140
Jan 9 0550 88 129
Jan 8 1415 63 99
Jan 8 1055 59 100
Jan 8 0630 36 75
Jan 8 0350 38 74
* Results charted within minutes of each other
Case #3Metabolic Status
Alk Phos 374 U/L
ALT 407 U/L
AST 2697 U/L
Total Bili 5.4 mg/dL
Lipase 2347 U/L
CK 863 U/L
Creatinine 4.7 mg/dL
TnI 0.5 ng/mL
Calcium 5.5 mg/dL
i Calcium 0.71 mmol/L
Anion gap 24
PT 32.8 sec
INR 3.0
Lactic Acid 10.7 mmol/L
Accu-Chek Comfort Curve Strip
Known Interferences
Galactose
Maltose
Xylose
Bilirubin (> 20 mg/dL)
Lipemia (> 5000 mg/dL)
Acetaminophen
(> 8 mg/dL)
Uric acid
Low Hct (< 20%)
High Hct
> 65% @ ≤ 200 mg/dL
> 55% @ > 200 mg/dL
Mannitol
Icodextrin
60 mg/dL glucose concentration
500 mg/dL glucoseconcentration
Clinica Chimica Acta 356 (2005) 178-183.
Crit Care Med 2005 Vol 33, no.12.
CAPILLARY BLOOD GLUCOMETER VS REFERENCE STANDARD
Crit Care Med 2005 Vol 33, No 12
ARTERIAL BLOOD GLUCOMETER AND REFERENCE STANDARD
Chest 2005: 127:1749-1751.
meters originally designed to test glucose in diabetics with normal hematocrit
ICU patients may suffer from multiple metabolic +/or hematologic derangements
ICU patients may be treated with multiple drugs
Results which do not seem realistic in
view of the clinical assessment should
be repeated in the Core Laboratory.
POC Glucose
Urine Drug ScreenImmunoassay
Does it detect oxycodone?
Basic urine drug immunoassay testing for opiates tests primarily for morphine (heroin and codeine metabolized to morphine).
These tests do not generally detect low to moderate oxycodone use.
STAT Quantitative Serum Toxicology Assays Required to Support the ED
acetaminophen co-oximetry ETOH
lithium digoxin MEOH
salicylate phenobarbital ethylene glycol
theophylline iron
valproic acid transferrin
Oxycodone
To detect compliance, abuse or toxicity
best detected by specific assay detection levels < 100ug/L necessary
Urine Drug Screen Immunoassay
Drug X-reaction
PCP Dextromethorphan, diphenhydramine, sertraline
Opiates Quinolone antibiotics
Amphetamines Detects all types of sympathomimetic amines (including those in OTC diet suppressants and cold medications)