ASSENT-4 PCI: Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction

ASSENT-4 PCI: Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction

Prior studies and a systematic review of large, randomized trials have shown that percutaneous coronary intervention (PCI) in the acute phase of myocardial infarction (MI) is superior to thrombolytic therapy. However, time delays for primary PCI are not insignificant and, as a consequence, only a minority of patients are actually treated within the 90-minute window recommended by current guidelines. Furthermore, previous studies have shown that early administration of fibrinolytic therapy is helpful and may be as efficacious as primary PCI.

The Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction (ASSENT)-4 PCI study was intended to be a large, randomized trial in acute MI patients facing very long delays (3-4 hours) before receiving therapy, as is typical for patients facing long travel distances or who must be transferred to a hospital with interventional facilities. The results of this study, including subanalyses, are presented below.

Study Design

ASSENT-4 PCI was designed to determine whether immediate fibrinolysis prior to delayed PCI would mitigate the negative impact of that delay and improve clinical outcomes. It was an open-label, 1:1 study that randomized patients to either full-dose full-dose tenecteplase (TNK-tPA) plus PCI (facilitated PCI) or to primary PCI with unfractionated heparin. PCI was to be performed between 60 and 180 minutes after randomization. Glycoprotein IIb/IIIa inhibitors were used either as a bail-out situation in patients pretreated with fibrinolytic therapy or at the investigators' discretion in the PCI-alone arm. Clopidogrel was administered only to patients who underwent stent implantation in both groups.

Primary Endpoint

Death, cardiogenic shock, or congestive heart failure within 90 days.

Inclusion Criteria

• Symptom onset within 6 hours prior to randomization
  
  
• Intention to perform primary PCI
  
  
• ST-segment elevation summation with a total of ≥ 6 mm

ASSENT-4 PCI: 90-Day Clinical Outcomes

Presenter: Frans Van de Werf, MD, PhD (University Hospital Gasthuisberg, Leuven, Belgium) on behalf of the ASSENT-4 PCI Investigators

In the study, which took place in 24 countries between November 2003 and April 2005, a total of 1667 patients were randomized to either facilitated PCI (n = 829) or PCI alone (n = 838) . The study was prematurely stopped by the Data and Safety Monitoring Board (DSMB) due to a significant disadvantage in patients randomized to the facilitated-PCI arm.

Time of onset of pain to randomization was similar in the facilitated-PCI and PCI-alone groups (135 vs 140 minutes, respectively; P = .55). There was a 7-minute difference between randomization to first balloon in favor of patients treated with PCI alone, but the difference did not reach statistical significance (115 vs 107 minutes, P = .69). In addition, a significantly larger percentage of patients in the PCI-only arm were concomitantly treated during the procedure with glycoprotein IIb/IIIa inhibitors (50.4% vs 9.5%, respectively; P < .0001).

The primary endpoint (death, cardiogenic shock, or congestive heart failure within 90 days) was significantly lower in the PCI alone group compared with the facilitated-PCI arm (13.7% vs 18.8%, respectively; P = .0055). Other individual endpoints also favored the PCI alone arm (Table). The significantly higher rate of stroke at 90 days in the facilitated-PCI group was mainly due to a significant increase in the rate of intracranial hemorrhage (Table).

Table. Individual Endpoints at 90 Days

Endpoint	TNK + PCI (n = 829)	PCI Alone (n = 838)	P Value)
Death (%)	6.7	5.0	.14
CHF (%)td>	12.1	9.4	.08
Cardiogenic shock (%)	6.1	4.8	.27
Reinfarction (%)	6.1	3.5	.02
Repeat TVR (%)	6.6	3.6	.006
Rehospitalization (for cardiogenic shock) (%)	0	0.1	1
Rehospitalization for other cardiac reasons (%)	10.5	11	.75
Total stroke (%)	1.81	0	.004
Intracranial hemorrhage (%)	0.97	0	.03
Ischemic stroke (%)	0.6	0	< .0001

CHF = congestive heart failure; PCI = percutaneous coronary intervention; TNK = full-dose tenecteplase; TVR = target vessel revascularization

In addition, in-hospital major bleeding complication rates were similar in both the facilitated-PCI and PCI-only groups (5.7% vs 4.3%, respectively; P = .22), but there was a significantly higher rate of minor bleeding complications in patients treated with facilitated PCI (25.2% vs 18.9%, P = .002).

Conclusions

1. In this prematurely terminated trial, the incidence of the combined clinical endpoint of death, congestive heart failure, or shock at 90 days was significantly higher in the facilitated-PCI arm than in the PCI-alone arm.
   
   
2. The stroke rate in the facilitated-PCI arm was consistent with previous TNK trials but surprisingly low in the PCI-alone arm.
   
   
3. Repeat target vessel revascularization and re-infarction were also reported more often in the facilitated-PCI arm.
   
   
4. Therefore, a strategy of routine, immediate PCI following full-dose lytic, as used in this study population and with this protocol, cannot be recommended.

ASSENT-4 PCI: Subgroups and Angiography Analyses

Presenter: Allan M. Ross, MD (George Washington University Medical Center, Washington, DC)

The results presented by Dr. Ross focused on different subgroup analyses of this study.

Time to Therapy. Patients randomized to TNK had a 10-minute delay from randomization to treatment, whereas patients randomized to PCI alone had a delay of 107 minutes from randomization to first balloon. Therefore, there is a 97-minute difference between the 2 groups.

Mortality Over Time. Mortality was stable across different time periods in patients randomized to facilitated PCI, whereas in patients randomized to PCI alone, it increased between the time when the DSMB stopped the trial, at 30-day analysis, and at 90-day analysis (Figure 1).

Figure 1. Evolution of mortality.

Enrollment Site. Enrollment was performed mainly at hospitals with PCI facilities (46%); 35% of patients were enrolled in a non-PCI hospital, and 19% of patients were randomized in the ambulance.

Time From Onset of Pain to Randomization by Enrollment Site. The shortest time from pain to randomization was in patients randomized in the ambulance (105 minutes), whereas the longest was in hospitals with PCI facilities (160 minutes). In hospitals without PCI facilities, the time from pain to randomization was 130-135 minutes. Similar trends were observed in the time period from randomization-to-balloon time (ambulance 98 minutes; hospital with PCI facilities 140 minutes; and hospital without PCI facilities 95 minutes). Randomization time to thrombolysis was similar in the 3 groups (10-12 minutes).

Mortality by Site of Enrollment. Patients randomized at a hospital with a PCI facility and treated with facilitated PCI had the highest mortality, whereas the rate was lowest in patients randomized in the ambulance to facilitated PCI (Figure 2).

Figure 2. Mortality by site of enrollment.

Mortality by age was similar regardless of the treatment assignment.

Mortality by gender. Mortality in female patients treated with TNK plus PCI was almost double that of their male counterparts (Figure 3).

Figure 3. Gender and mortality.

Figure 3.

Mortality by Site of Infarct. Patients with anterior wall infarction and treated with TNK plus PCI had higher mortality rates than those treated with PCI alone.

TIMI-3 Coronary Blood Flow. Normal TIMI-3 coronary blood flow at the diagnostic coronary angiography was observed in 43.5% of patients pretreated with TNK vs only 15.1% of patients treated with PCI alone. The rate of normal TIMI 3 coronary blood flow was highest in patients who underwent randomization and were treated in the ambulance (55%) and lowest in those treated at a PCI-facility hospital (33%). Following the procedure, a similar percentage of patients had achieved normal coronary blood flow (88%).

Conclusions

1. Time intervals, place of enrollment, and lower than expected reperfusion rates in the facilitated-PCI group provide some insight into the results of this study.
   
   
2. It remains unclear what impact fibrinolysis would have on outcomes in MI patients with truly long delays before intended PCI.

Commentary

ASSENT-4 PCI provides important data regarding facilitated PCI. The concept of initiating lytic therapy in patients who cannot undergo immediate PCI for a variety of reasons (lack of facility, lack of personnel, busy cath lab, etc) while they wait for intervention is appealing and seems to make sense. But like so many hypotheses in medicine, they do not always reflect reality. Patients treated with TNK prior to PCI had worse outcomes (increased stroke and mortality) than those patients who underwent PCI alone, to the extent that the DSMB had to stop recruitment.

The subgroup analyses presented by Dr. Ross are provocative and raise more questions regarding patients who may actually derive some benefit from this treatment (eg, those who receive treatment in the ambulance) vs those who may not (eg, female patients, those with anterior wall infarctions).

This study is in concordance with the Abciximab Before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-term Follow-up (ADMIRAL)^[1] trial, in which patients pretreated with abciximab in the ambulance actually derived the most benefit, whereas patients treated on-site did not.

The implications and the logistics of such treatment are complicated and would need to be assessed in a dedicated study.

Source:

http://www.medscape.com/viewarticle/517566

Note: Some figures are not visible clearly. View them from original source.

The FINESSE and CARESS in AMI Trials: Is Facilitated PCI Ready for Prime Time?

Posted 12/20/2007

Luis Gruberg, MD, FACC
Author Information

Introduction

There are an estimated 500,000 new acute, ST-segment elevation myocardial infarctions (STEMI) events in the United States each year. A series of landmark studies has shown that prompt opening of the infarct-related artery is the treatment of choice in patients with STEMI, and this can be achieved either with drugs (lytics) or using a mechanical approach, such as percutaneous coronary intervention (PCI). Rapid reperfusion in combination with adequate pharmacologic treatment has been shown to reduce infarct size, minimize myocardial damage, and therefore decrease mortality rates in these patients. Primary PCI has been shown to be a superior strategy compared with lytics when performed in a timely fashion (less than 90 minutes) by an experienced team. However, 60% to 70% of STEMI patients present to hospitals that are not equipped with the facilities to perform primary PCI. Therefore, only a minority of patients will undergo PCI (diagnosis to balloon time) in less than 90 minutes.

According to the American College of Cardiology/American Heart Association (ACC/AHA) STEMI Guidelines,^[1] lytics are still considered a viable option in patients who present less than 3 hours from symptom onset, especially in instances when an invasive strategy may be delayed beyond the recommended time or when there is no such option. Patients who present after 3 hours to a hospital without PCI facilities can either be transferred to another hospital or be treated with lytics. An obvious offshoot of this approach has been the administration of lytics followed immediately by transfer for planned PCI, known as facilitated PCI. The rationale to this approach is that a significant proportion of patients would undergo recanalization of the infarct-related artery prior to PCI.

A number of studies have evaluated this pharmacoinvasive approach; one of the most important and most recent was the Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction (ASSENT)-4 PCI.^[2] This trial was designed to determine whether immediate fibrinolysis prior to delayed PCI would mitigate the negative impact of that delay and improve clinical outcomes. ASSENT-4 PCI was an open-label, 1:1 study that randomized patients to either full-dose tenecteplase (TNK-tPA) plus PCI (facilitated PCI) or to primary PCI with unfractionated heparin. PCI was to be performed between 60 and 180 minutes after randomization.^[3] The study was terminated prematurely due to worse outcomes in patients randomized to the facilitated arm. The primary endpoint (death, cardiogenic shock, or congestive heart failure within 90 days) was significantly higher in the facilitated-PCI arm compared with the PCI alone group (18.8% vs 13.7%, respectively; P = .0055) (see Related Links). Other individual endpoints also favored the PCI-alone arm. However, other studies, such as Which Early ST-elevation Myocardial Infarction Therapy (WEST)^[3] study and the Leipzig experience,^[4] showed conflicting results. The mixed results between these studies warranted additional randomized trials.

At the recently held European Society of Cardiology 2007 World Congress in Vienna, Austria (see Related Links), 2 new important studies that assessed the role of facilitated PCI were presented: the FINESSE and CARESS in AMI trials. They are described below.

Final Results of the FINESSE Trial

Presenter: Stephen Ellis, MD, The Cleveland Clinic (Cleveland, Ohio), for the FINESSE Investigators

FINESSE Study Design

The Facilitated Intervention With Enhanced Reperfusion Speed to Stop Events (FINESSE) trial enrolled patients with a new STEMI within 6 hours of pain onset with estimated time to cath lab of 1-4 hours. Patients were randomized in a double-blind, double-dummy fashion to either 1 of 3 treatment strategies:

Primary PCI; Facilitated PCI with abciximab alone; or Facilitated PCI with reteplase/abciximab.

Patients were treated with aspirin and heparin and then transferred to the cath lab; patients in primary PCI received in-lab abciximab, and the facilitated PCI groups received placebo in the cath lab.

Primary endpoint: Composite at 90 days of all-cause mortality/rehospitalization for congestive heart failure, resuscitated ventricular fibrillation more than 48 hours after randomization, and cardiogenic shock.

Secondary endpoints:

Complications of MI through 90 days: o Rehospitalization for congestive heart failure o Resuscitated ventricular fibrillation o Cardiogenic shock All-cause mortality through 90 days Percentage of patients with ST-segment resolution > 70% at 60-90 minutes

Safety endpoints:

Major and minor bleeding Intracranial bleeding Stroke Transfusions Thrombocytopenia

Results

Study enrollment was stopped due to budgetary issues in December 2006 after 2452 patients were entered into the study. A total of 1693 patients were enrolled in the main study and 759 in the low-molecular-weight heparin substudy. Baseline characteristics are shown in Table 1 .

The average door-to-balloon time was 132 minutes. TIMI flow 2/3 prior to PCI was achieved in 61% of patients treated with reteplase/abciximab vs 25% in the primary PCI group and 26% in the placebo/abciximab group (Figure 1). TIMI flow 2/3 at the end of the procedure was achieved in 98% to 99% of patients in all 3 groups, and the rate was significantly higher in the reteplase/abciximab group compared with the abciximab facilitated PCI group (P = .04) (Figure 2). ST-segment resolution (> 70%) prior to balloon inflation was significantly better in patients treated with reteplase/abciximab. However, at 60-90 minutes after balloon inflation, ST-segment resolution was similar in all groups (Figure 3).

Figure 1. (click image to zoom) FINESSE: TIMI flow in infarct-related artery before PCI.

Figure 2. (click image to zoom) FINESSE: TIMI flow in infarct-related artery after PCI.

Figure 3. (click image to zoom) FINESSE: ST-segment resolution before and after PCI.

At 90 days, there was no difference in the primary composite endpoint between the 3 groups ( Table 2 ). There was also no difference in the rate of major secondary endpoints between the groups. However, total amount of TIMI bleeding complications was significantly higher in the facilitated PCI arms. There was also a higher rate of intracranial hemorrhage in the reteplase/abciximab group compared with the other 2 groups, but the difference was not significant.

FINESSE Conclusions

There was no significant improvement in the primary endpoint or its components in patients treated with either abciximab-facilitated PCI or reteplase/abciximab-facilitated PCI compared with primary PCI with administration of abciximab in the cath lab. Reteplase/abciximab administered early was associated with an increase in pre-PCI TIMI 3 flow and > 70% ST-segment resolution at 60-90 minutes. Post-PCI TIMI 3 flow and ST resolution at 180-240 minutes was similar in all 3 treatment groups. There was a significant increase in major and minor bleeding complications in the facilitated PCI groups. There was no increase in total stroke rate; however, there was an increase in the rate of intracranial hemorrhage in the reteplase/abciximab group. Therefore, primary PCI with in-lab abciximab administration provides better benefit/risk profile than the 2 facilitated strategies in patients with STEMI who can undergo PCI within 4 hours of first medical contact.

Clinical Outcomes in the CARESS in AMI Trial

Presenter: Carlo Di Mario, MD, PhD, Royal Brompton Hospital and Imperial College (London, United Kingdom), on behalf of the CARESS in AMI Investigators

The Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) study compared a strategy of early transfer of patients to a PCI center after thrombolysis vs medical treatment continued in the admitting hospital and transfer for rescue PCI only if there was evidence of lack of reperfusion. Patients less than 12 hours from symptom onset and with STEMI were randomized to either:

Facilitated PCI (lytics and transfer to the nearest PCI center); or Medical treatment/rescue (lytics and transfer for rescue PCI if persistent ST elevation).

All patients were treated with aspirin, clopidogrel (started in the cath lab), heparin, reteplase, and abciximab.

Primary outcome: Death/reinfarction/refractory ischemia at 30 days.

CARESS in AMI Results

A total of 600 patients were randomized to facilitated PCI (n = 297) or to the medical/rescue (n = 300) arms of the study. The time from pain onset to reteplase treatment was 169-171 minutes. The time from reteplase administration to PCI was 136 minutes in the facilitated arm vs 212 minutes in the rescue arm. Baseline characteristics of patients enrolled in the study are shown in Table 3 .

Prior to PCI, TIMI 3 flow was observed in 60% of patients, and after the procedure, TIMI 3 flow was seen in 91% of patients. The length of hospital stay was greater in the medical/rescue arm. Only 55% of patients in the rescue arm were treated with a thienopyridine vs 85% in the facilitated arm. The combined endpoint of death/reinfarction/refractory ischemia at 30 days was significantly lower in the facilitated arm compared with the medical/rescue-treated patients (4.1% vs 11.1%, respectively; P = .001) ( Table 4 ). The individual endpoints are shown in Table 4 . Safety outcomes showed a significantly higher rate of bleeding complications in the facilitated arm of the study .

CARESS in AMI Conclusions

Facilitated PCI yields a 63% proportional reduction of the composite endpoint of death, reinfarction, and refractory ischemia. The reduction in risk in the facilitated PCI group was driven largely by refractory ischemia, but there were favorable trends for death and reinfarction. Event reduction was achieved despite the use of rescue PCI in more than one third of patients in the control group. This trial confirms and expands the indication of the ESC guidelines to early angioplasty after lysis, suggesting that high-risk STEMI patients should be immediately transferred for PCI after lysis.

Viewpoint

On the basis of results obtained from these 2 important studies, at the present time we cannot make a clear-cut recommendation regarding the routine use of facilitated PCI in patients with STEMI. ASSENT-4 and FINESSE -- 2 very well-designed, important, and large studies -- failed to show a benefit, and results from ASSENT-4 suggest that the strategy may even yield a harmful effect. However, we cannot ignore the fact that in both studies a significantly higher percentage of patients achieved reperfusion (TIMI 2/3) in the infarct-related artery by the time they arrived to the cath lab. This is a critical observation when we consider that time is muscle. However, these findings still leave us questioning why the improved reperfusion rates did not translate to improved clinical outcomes. Possible explanations include an increase in bleeding complications, the lack of adequate antithrombotic/antiplatelet adjuvant therapy in ASSENT-4, or that perhaps these studies were underpowered to show a clinical benefit in a short period of time (30-90 days). Will the beneficial effect be evident at long-term follow-up?

The current guidelines of the ACA/AHA/SCAI for PCI have classified facilitated PCI as a Class IIb indication and stipulate that the technique could be performed as a reperfusion strategy in higher-risk patients when PCI is not immediately available and bleeding risk is low (Level of Evidence: B).^[5] Although we may be somewhat reluctant, at the present time there is no clear indication for the routine use of facilitated PCI in STEMI patients, with the exception of high-risk patients in whom a long delay may be expected prior or during transport to a PCI facility.

Source: http://www.medscape.com/viewarticle/563069_1

ACC/AHA/SCAI Updated PCI Guidelines

ACC/AHA/SCAI Updated PCI Guidelines

In November 2005, the ACC/AHA/SCAI jointly presented a major update of the Guidelines on Percutaneous Coronary Interventions (PCI). This document is a comprehensive analysis of the techniques, medications, and devices that have advanced the delivery of PCI since 2001, when the ACC/AHA last released guidelines on the topic. In my view, the updated guidelines are greatly strengthened by the equal participation of SCAI in their development. Four SCAI leaders - Drs. Ted Feldman, John Hirshfeld, Jr., Morton Kern, and Douglass Morrison - participated on the writing committee, ensuring that the document benefits from the detailed focus of cardiovascular interventionalists as well as the broad view of generalists. The result sets forth goals for optimal treatment of the many patients who are eligible for, and undergo, PCI procedures. Key new recommendations include the following:

* Door-to-balloon time for primary PCI of 90 minutes or less

* Annual operative volumes for PCI (> 75 elective PCI procedure with at least 11 on acute myocardial infarction patients annually) and high-volume facilities (more than 400 procedures annually)

* Broadened anatomic indicators for patients eligible for PCI - most notably, PCI for patients with left main coronary artery disease who are ineligible for coronary artery bypass graft surgery

* Monitoring and managing patients who have undergone PCI, including risk-factor modification for all patients; a regimen of aspirin and clopidogrel for most patients; ACE inhibitors for patients with coronary artery disease, left ventricular dysfunction, or hypertension; at least 6 months on beta-blockers for AMI or other acute conditions; aggressive lipid lowering for high-risk patients; and, for diabetic patients, glucose-lowering therapies aimed at bring HbA1c levels to less than seven percent

The updated guidelines examine closely the latest data on two of the most exciting advances in PCI: drug-eluting stents (DES) and distal embolic protection devices. While stressing the need for long-term study of both, the guidelines recommend DES in many settings, including diabetic patients, patients with longer lesions and smaller diameter vessels. Distal-protection devices have been recommended in this update specifically for patients who are undergoing PCI to saphenous vein grafts; to date their efficacy in AMI patients undergoing primary PCI has not been shown.

Perhaps the most controversial recommendation in the 2005 guidelines is that elective PCI should not be performed at facilities that do not have onsite cardiac surgery facilities. While SCAI supports this 2005 Guideline Update in general, the Society recognizes the reality that such an approach has developed in multiple locations both in the United States and other regions of the world. The Society feels that discussion of this important subject should ultimately revolve around what is in the best interest of the patient. Currently SCAI is assembling information on this important subject so that discussion can be focused on the true risks and benefits of this approach within the realities of each health care system.


Source:
http://www.medscape.com/viewarticle/524270

Note: This is a review article. For detailed version, click on following link:

http://www.chestjournal.org/cgi/reprint/126/3_suppl/172S

Typical Lab Values from NBME !!

I prefer the term "Typical" to describe laboratory values. Using the word "Normal" implies that someone falling outside of the given range is "Abnormal" ... and I do not think that is a term that a health care provider should present to their patients.

Typical “Normal” Laboratory Values that appear on the USMLE Step 1 provided by the NBME.

TYPICAL “Normal” LABORATORY VALUES

REFERENCE RANGE SI REFERENCE INTERVALS

BLOOD, PLASMA, SERUM

* Alanine aminotransferase (ALT, GPT at 30 C) 8-20 U/L 8-20 U/L

Amylase, serum 25-125 U/L 25-125 U/L

* Aspartate aminotransferase (AST, GOT at 30 C) 8-20 U/L 8-20 U/ L

Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL 2-17 μmol/L // 0-5 μmol/L

* Calcium, serum (Ca²⁺) 8.4-10.2 mg/dL 2.1-2.8 mmol/L

* Cholesterol, serum Rec:<200> <5.2>

Cortisol, serum 0800 h: 5-23 μg/dL 138-635 nmol/L

1600 h: 3-15 μg/dL 82-413 nmol/L

2000 h: ≤ 50% of 0800 h Fraction of 0800 h: ≤ 0.50

Creatine kinase, serum Male: 25-90 U/L 25-90 U/L

Female: 10-70 U/L 10-70 U/L

* Creatinine, serum 0.6-1.2 mg/dL 53-106 μmol/L

Electrolytes, serum

Sodium (Na⁺) 136-145 mEq/L 136-145 mmol/L

Chloride (Cl^-) 95-105 mEq/L 95-105 mmol/L

* Potassium (K⁺) 3.5-5.0 mEq/L 3.5-5.0 mmol/L

Bicarbonate (HCO₃^-) 22-28 mEq/L 22-28 mmol/L

Magnesium (Mg²⁺) 1.5-2.0 mEq/L 1.5-2.0 mmol/L

Estriol, total, serum (in pregnancy)

24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 104-590 // 208-970 nmol/L

28-32 wks // 36-40 wks 40-220 ng/mL // 80-350 ng/mL 140-760 // 280-1210 nmol/L

Ferritin, serum Male: 15-200 ng/mL 15-200 μg/L

Female: 12-150 ng/mL 12-150 μg/L

Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL 4-25 U/L

Female: premenopause 4-30 mIU/mL 4-30 U/L

midcycle peak 10-90 mIU/mL 10-90 U/L

postmenopause 40-250 mIU/mL 40-250 U/L

Gases, arterial blood (room air)

pH 7.35-7.45 [H⁺] 36-44 nmol/L

pCO₂ 33-45 mm Hg 4.4-5.9 kPa

pO₂ 75-105 mm Hg 10.0-14.0 kPa

* Glucose, serum Fasting: 70-110 mg/dL 3.8-6.1 mmol/L

2-h postprandial: <> <>

Growth hormone – arginine stimulation Fasting: <> <>

provocative stimuli: > 7 ng/mL > 7 μg/L

Immunoglobulins, serum

IgA 76-390 mg/dL 0.76-3.90 g/L

IgE 0-380 IU/mL 0-380 kIU/L

IgG 650-1500 mg/dL 6.5-15 g/L

IgM 40-345 mg/dL 0.4-3.45 g/L

Iron 50-170 μg/dL 9-30 μmol/L

Lactate dehydrogenase, serum 45-90 U/L 45-90 U/L

Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL 6-23 U/L

Female: follicular phase 5-30 mIU/mL 5-30 U/L

midcycle 75-150 mIU/mL 75-150 U/L

postmenopause 30-200 mIU/mL 30-200 U/L

Osmolality, serum 275-295 mOsmol/kg 275-295 mOsmol/kg

Parathyroid hormone, serum, N-terminal 230-630 pg/mL 230-630 ng/L

* Phosphatase (alkaline), serum (p-NPP at 30 C) 20-70 U/L 20-70 U/L

* Phosphorus (inorganic), serum 3.0-4.5 mg/dL 1.0-1.5 mmol/L

Prolactin, serum (hPRL) <> <>

* Proteins, serum

Total (recumbent) 6.0-7.8 g/dL 60-78 g/L

Albumin 3.5-5.5 g/dL 35-55 g/L

Globulin 2.3-3.5 g/dL 23-35 g/L

Thyroid-stimulating hormone, serum or plasma 0.5-5.0 μU/mL 0.5-5.0 mU/L

Thyroidal iodine (¹²³I) uptake 8-30% of administered dose/24 h 0.08-0.30/24 h

Thyroxine (T₄), serum 5-12 μg/dL 64-155 nmol/L

Triglycerides, serum 35-160 mg/dL 0.4-1.81 mmol/L

Triiodothyronine (T₃), serum (RIA) 115-190 ng/dL 1.8-2.9 nmol/L

Triiodothyronine (T₃), resin uptake 25-35% 0.25-0.35

* Urea nitrogen, serum (BUN) 7-18 mg/dL 1.2-3.0 mmol urea/L

* Uric acid, serum 3.0-8.2 mg/dL 0.18-0.48 mmol/L

CEREBROSPINAL FLUID

Cell count 0-5 cells/mm³ 0-5 x 10⁶/L

Chloride 118-132 mEq/L 118-132 mmol/L

Gamma globulin 3-12% total proteins 0.03-0.12

Glucose 40-70 mg/dL 2.2-3.9 mmol/L

Pressure 70-180 mm H₂O 70-180 mm H₂O

Proteins, total <40> <0.40>

HEMATOLOGIC

Bleeding time (template) 2-7 minutes 2-7 minutes

Erythrocyte count Male: 4.3-5.9 million/mm³ 4.3-5.9 x 10¹²/L

Female: 3.5-5.5 million/mm³ 3.5-5.5 x 10¹²/L

Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h 0-15 mm/h

Female: 0-20 mm/h 0-20 mm/h

Hematocrit Male: 41-53% 0.41-0.53

Female: 36-46% 0.36-0.46

Hemoglobin A_1c ≤ 6% ≤ 0.06%

Hemoglobin, blood Male: 13.5-17.5 g/dL 2.09-2.71 mmol/L

Female: 12.0-16.0 g/dL 1.86-2.48 mmol/L

Hemoglobin, plasma 1-4 mg/dL 0.16-0.62 mmol/L

Leukocyte count and differential

Leukocyte count 4500-11,000/mm³ 4.5-11.0 x 10⁹/L

Segmented neutrophils 54-62% 0.54-0.62

Bands 3-5% 0.03-0.05

Eosinophils 1-3% 0.01-0.03

Basophils 0-0.75% 0-0.0075

Lymphocytes 25-33% 0.25-0.33

Monocytes 3-7% 0.03-0.07

Mean corpuscular hemoglobin 25.4-34.6 pg/cell 0.39-0.54 fmol/cell

Mean corpuscular hemoglobin concentration 31-36 % Hb/cell 4.81-5.58 mmol Hb/L

Mean corpuscular volume 80-100 μm³ 80-100 fl

Partial thromboplastin time (activated) 25-40 seconds 25-40 seconds

Platelet count 150,000-400,000/mm³ 150-400 x 10⁹/L

Prothrombin time 11-15 seconds 11-15 seconds

Reticulocyte count 0.5-1.5% of red cells 0.005-0.015

Thrombin time <2> <2>

Volume

Plasma Male: 25-43 mL/kg 0.025-0.043 L/kg

Female: 28-45 mL/kg 0.028-0.045 L/kg

Red cell Male: 20-36 mL/kg 0.020-0.036 L/kg

Female: 19-31 mL/kg 0.019-0.031 L/kg

SWEAT

Chloride 0-35 mmol/L 0-35 mmol/L

URINE

Calcium 100-300 mg/24 h 2.5-7.5 mmol/24 h

Chloride Varies with intake Varies with intake

Creatine clearance Male: 97-137 mL/min

Female: 88-128 mL/min

Estriol, total (in pregnancy)

30 wks 6-18 mg/24 h 21-62 μmol/24 h

35 wks 9-28 mg/24 h 31-97 μmol/24 h

40 wks 13-42 mg/24 h 45-146 μmol/24 h

17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h 8.2-27.6 μmol/24 h

Female: 2.0-8.0 mg/24 h 5.5-22.0 μmol/24 h

17-Ketosteroids, total Male: 8-20 mg/24 h 28-70 μmol/24 h

Female: 6-15 mg/24 h 21-52 μmol/24 h

Osmolality 50-1400 mOsmol/kg

Oxalate 8-40 μg/mL 90-445 μmol/L

Potassium Varies with diet Varies with diet

Proteins, total <> <>

Sodium Varies with diet Varies with diet

Uric acid Varies with diet Varies with diet

*Included in the Biochemical Profile (SMA-12). By chance alone, at least one false-positive result is expected in almost half the people having 12 tests (SMA-12) and in two thirds of those having 20 tests (SMA-20).

SMA-6 (6 tests) – bicarbonate, chloride, glucose, potassium, sodium, urea nitrogen

SMA-12 (12 tests) – bicarbonate, calcium, chloride, cholesterol, creatinine, glucose, phosphatase (alkaline), potassium, sodium, transaminases (alanine and aspartate), urea nitrogen

SMA-20 (20 tests) – protein (albumin), bicarbonate, bilirubin (direct and total), calcium, chloride, cholesterol, creatinine, gamma-glutamyltransferase, glucose, lactic dehydrogenase, magnesium, phosphatase (alkaline), potassium, protein (total), sodium, transaminases (alanine and aspartate), urea nitrogen, uric acid

Typical “Normal” Laboratory Values that appear on the USMLE Step 1 provided by the NBME .