the Five Point Peripheral Blood Screen for HANTAVIRUS CARDIOPULMONARY SYNDROME - PowerPoint Presentation

Slide1

the Five Point Peripheral Blood Screen for HANTAVIRUS CARDIOPULMONARY SYNDROME

Glynnis Ingall MD, PhD

Slide2

Hantavirus Cardiopulmonary Syndrome

Hantavirus

Cardiopulmonary

Syndrome (

HCPS

) is a severe, sometimes fatal, respiratory disease

caused

by infection

with hantavirus

Relatively short febrile prodromal period (with chills and myalgia) lasting 3-5 days. Nonspecific

symptoms similar to other viral infections

Slide3

Rapid Screening for Hantavirus Cardiopulmonary Syndrome (HCPS)Challenges

HCPS: Patients may have rapid clinical progression

Need for prompt recognition and referral of severe cases to facility where advanced intensive care services are available.

Specificity: Patients who are developing HCPS often initially present with clinical features similar to other viral or flu-like illnesses

Need for a test that will alert providers to possibility of hantavirus infection

Rapid serologic tests for detection of hantavirus antibodies are not yet available

Currently it takes 12-24 hours to perform antibody testing including transport time to laboratory in Albuquerque.

Slide4

A Rapid Screening Test for HCPS in Rural

A

reas

Desired Features

Can

be performed with routinely available laboratory

equipment

Can be performed

by non-specialized laboratory technical

staff

Feasibility to train staff on all shifts and to maintain competency

Can be performed without adversely affecting laboratory workflow

Provides reliable information that supports clinical decision making.

Slide5

Development of the 5 Part Hanta Virus Peripheral Blood Screen

Koster

, F.

Foucar

, K.

Hjelle

, B. et al; Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood

Smear Review;

American Journal of Clinical Pathology;

2001,

volume 116; p 665 – 672.

Slide6

UNM-Five Part Peripheral Blood Screen for HCPS

Purpose: To identify a rapid method for presumptive diagnosis of HCPS using peripheral blood counts and smear morphology review.

Compared peripheral blood findings of 52 cases of HCPS to 128 control subjects who where

sero

-negative for hantavirus but clinically mimicked HCPS in prodromal or cardiopulmonary phase.

They found an aggregate of five peripheral blood findings which were sensitive and specific enough to allow a presumptive diagnosis of HCPS.

Slide7

Development of the 5 Part Hantavirus Peripheral Blood ScreenUNMH implemented a rapid screening tool for the triage of patients with suspected HCPS using the 5 point peripheral blood scoring system.

4 out of 5 cutoff:

Sensitivity of 96%,

S

pecificity of 99% - missed no patients requiring intensive care

Thrombocytopenia is an early indicator of infection (often seen in prodromal phase)

Proposed that the scoring system be used to guide early treatment and patient transport decisions until a rapid, specific, serologic test became widely available.

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Five Point Peripheral Blood Scoring for HCPSThrombocytopenia

Left shift in neutrophils

Hemo

-concentration (

Hb

/

Hct

elevated for age and gender)

Lack of significant toxic granulation

Immunoblasts

and plasma cells constituting more than 10% of lymphocytes

Note: Value

of this scoring system

verified

with additional decade of

use:

Dvorscak

, L. and

Czuchlewski

, D. R. “Successful Triage of Suspected Hantavirus

Cadiopulmonary

Syndrome By Peripheral Blood Smear Review

AM J

Clin

Pathol

2014;142:196-201

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Hantavirus Peripheral Blood Screen

The five variables used in the scoring system, individually, can be positive in other clinical conditions. Scoring for all five factors and using a cutoff of a score of four or five out of five increases the specificity for HCPS.

Note: If HCPS is an ongoing clinical consideration and hantavirus score is equivocal, then serial testing could be offered (8-12 hour intervals).

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HCPS - Platelets

In about 80% of individuals with

HCPS

, the platelet count is below

150,000.

A dramatic fall in the platelet count may herald a transition from the

prodromal

to the pulmonary edema phase of the illness.

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Platelets

Note: Thrombocytopenia is not uncommon in viral illness therefore this factor alone is not specific for HCPS

Thrombocytopenia can be seen in other infections (sepsis, plague, tularemia,

borreliosis

, Rocky Mountain spotted fever, and parvovirus) as well as in other noninfectious conditions

Slide12

HCPS-Elevated Hb

/

Hct

for age and

gender

Hemoconcentration

:

A rise in the hematocrit may indicate a fluid shift from the patient's circulation into the lungs in patients with HCPS.

Note:

When evaluating the significance of the

hemoconcentration

, the clinician should be aware of other pre-existing causes of

erythrocytosis

such as chronic pulmonary disease.

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HCPS – Left Shift in Neutrophil Series and Lack of Significant Toxic Granulation

In HCPS, the

white blood cell count tends to be raised with a left shift.

However, toxic granulation is negligible or absent.

Note: In bacterial infections with elevated white count and left shift, toxic changes are prominent.

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HCPS- Immunoblasts/Plasma cells Greater than 10% of Lymphocytes

I

mmunoblasts

/plasma cells

are frequently present, usually at the time of onset of pulmonary

edema. (Numbers tend to decline during convalescence)

Notes:

Immunoblasts

alone are not specific for HCPS.

They are seen in peripheral blood smears in small numbers as the result of transient immune response of diverse etiologies.

Slide15

Hantavirus Peripheral Blood Screen

Scoring System

 

1.

Hgb

/

Hct

elevated for gender/age

Yes

No

2. Left shift of granulocytic series

Yes No

 

3. Absence of toxic

changes

Yes

No

4.

Thrombocytopenia

Yes

No

 

5.

Immunoblasts

& Plasma Cells > 10% of lymphocytes Yes No

Slide16

4-5 out of 5 C

riteria

Based upon the UNMH experience, the positive predictive value is 90% for cases fulfilling 4 of 5 criteria and greater than 90% for cases meeting 5 of 5 criteria

when the patient has other clinical features suggestive of Hantavirus cardiopulmonary syndrome. Serum specimen for serologic confirmation is indicated.

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3 out of 5 C

riteria

Blood

features are non-diagnostic at this

time

for

Hantavirus cardiopulmonary syndrome.

If

an early

Hantavirus infection

is still a clinical consideration, repeat peripheral

blood

screening

in 12 hours may be of value.

Slide18

1-2 out of 5

C

riteria

Blood

features are non-diagnostic at this

time.

Repeat

evaluation is recommended if clinically warranted.

Slide19

Limitations of Five Point Peripheral Blood Screen for HCPS

For the UNM study, the estimates of sensitivity and specificity were determined on a patient population with high pre-test probability of HCPS (Most patients in region with suspected HCPS are transferred to UNMH for advanced care).

The estimates of Positive Predictive Value of

this

test

would be substantially lower in parts of the country where hantavirus infection prevalence is low. Therefore, the screen would not be appropriate to perform in non-endemic areas.

Will the positive predictive value of the test be as high in the community setting where patients may be seeking care at an earlier stage of hantavirus infection or may have other pre-existing clinical conditions that may affect scoring system (cirrhosis, COPD

etc.)?

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Limitations: Continued

Hemato

-pathologist

vs.Technologist

Scoring

For

the UNM study, the hantavirus peripheral blood scores

were

determined by

hemato

-pathologists. The authors of the original paper were concerned

as to

whether this test could be performed by rural hospital technologists.

Note: Experience at TMC has shown that laboratory technologists (both 2yr and 4yr degreed) on all shifts and with varying years of work experience can perform these screens accurately and consistently after appropriate training.

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Limitations: Continued

Hantavirus testing not performed when indicated

Hantavirus peripheral blood screening may not be performed, even if available, if providers do not consider the possibility of hantavirus infection in patients presenting with flu-like febrile illness. This may be an issue with contract providers who were trained or primarily practice in non-endemic areas.

Reflex hanta virus screening for thrombocytopenia

In order identify patients with possible HCPS, consider adding a reflex hantavirus screen for ED or urgent care patients who present with thrombocytopenia and respiratory illness.

Note: At TMC, Four out of the five cases with high peripheral blood scores and IgM positive serology for hantavirus were discovered first by the lab due to reflex testing for thrombocytopenia.

Slide22

Limitations

Presumptive Diagnosis of HCPS

: Scoring system is a screening test for patients who may have hantavirus cardiopulmonary syndrome. It is a presumptive diagnosis supported by appropriate clinical and history findings. Confounding chronic clinical conditions may need to be considered when interpreting the significance of a given score.

Not a test for exposure to hantavirus:

Scoring system can not determine exposure to hantavirus or distinguish milder forms of hantavirus infection from other causes of viral illness.

Collect serum sample:

C

ollect

a sample for serologic confirmation when performing a hantavirus peripheral blood screen. Positive IgM antibodies for hantavirus suggests acute infection.

Slide23

SummaryCurrently, the hantavirus 5 part peripheral blood score is the only rapid screening test for patients who may be developing hantavirus cardio-pulmonary syndrome.

Implementation of this test at clinical labs in endemic area is feasible. No specialized equipment or staffing are required

Consider offering the test both as a provider-ordered and as a reflex for patients presenting to the ED or urgent care with thrombocytopenia.

For case follow-up:

C

ontact your state department of health and obtain a serology (serum) specimen for hantavirus IgG and IgM testing.

For information about clinical management of hantavirus cardio-pulmonary syndrome, call University of New Mexico Physician Access Line

at:

505 272-2000

.