Observation of Titers in HL7 Content

Several important diagnostic measures take the form of a Titer. Quoting from Wikipedia:

A titer (or titre) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive reading. For example, positive readings in the first 8 serial twofold dilutions translate into a titer of 1:256 (i.e., 2−8). Titers are sometimes expressed by the denominator only, for example 1:256 is written 256.

A specific example is a viral titer, which is the lowest concentration of virus that still infects cells. To determine the titer, several dilutions are prepared, such as 10−1, 10−2, 10−3, … 10−8.

So the higher the titer, the higher the concentration. 1:2 means a lower concentration than 1:128 (note that this means the clinical intent is the opposite of the literal numeric intent – as the titre gets lower, the concentration gets higher).

Titers are pretty common in clinical diagnostics – I found about 2600 codes for titer type tests in LOINC v2.48 (e.g. Leptospira sp Ab.IgG).

Representing Titers in HL7 Content

In diagnostic reports, titers are usually presented in the text narrative (or the printed form) using the form 1:64, since this makes clear the somewhat arbitrary nature of the numbers in the value. However it’s not unusual for labs to report just the denominator (e.g. “64”) and the person interpreting the reports is required to understand that this is a titer test (this is usually stated in the name).

When it comes to reporting a Titer in structured computable content, there’s several general options:

  • represent it as a string, and leave it up to the recipient to parse that if they really want
  • represent it as an integer, the denominator
  • use a structured form for representing the content

Each of the main HL7 versions (v2, CDA, and FHIR) offer options for each of these approaches:

String Integer Structured
V2 OBX||ST|{test}||1:64 OBX||NM|{test}||64 OBX||SN|{test}||^1^:^64
CDA <value xsi:type=”ST”> 1:64 </value> <value xsi:type=”INT” value=”1:64″/> <value xsi:type=”RTO_INT_INT”> <numerator value=”1”/> <denominator value=”64”> </value>
FHIR “valueString “ : “1:64” “valueInteger” : ”64” “valueRatio”: { “numerator” : { “value” : “1” }, “denominator” : { “value” : “64” } }

(using the JSON form for FHIR here)

One of the joys of titres is that there’s no consistency between the labs – some use one form, some another. A few even switch between representations for the same test (e.g. one LOINC code, different forms, for the same lab).

This is one area where there would definitely be some benefit – to saying that all labs should use the same form. That’s easy to say, but it would be really hard to get the labs to agree, and I don’t know what the path to pushing for conformance would be (in the US, it might be CLIA; in Australia, it would be PITUS; for other countries, I don’t know).

One of the problems here is that v2 (in particular) is ambiguous about whether OBX-5 is for presentation or not. It depends on the use case. And labs are much more conservative about changing human presentation than changing computable form – because of good safety considerations. (Here in Australia, the OBX05 should not be used for presentation, if both sender and receiver are fully conformant to AS 4700.2, but I don’t think anyone would have any confidence in that). In FHIR and CDA, the primary presentation is the narrative form, but the structured data would become the source of presentation for any derived presentation; this is not the primary attested presentation, which generally allays the lab’s safety concerns around changing the content.

If that’s not enough, there’s a further issue…

Incomplete Titers

Recently I came across a set of lab data that included the titer “<1:64”. Note that because the intent of the titre is reversed, it’s not perfectly clear what this means. Does this mean that titre was <64? or that the dilution was greater than 64. Well, fortunately, it’s the first. Quoting from the source:

There are several tests (titers for Rickettsia rickettsii, Bartonella, certain strains of Chlamydia in previously infected individuals, and other tests) for which a result that is less than 1:64 is considered Negative.  For these tests the testing begins at the 1:64 level and go up, 1:128, 1:256, etc.   If the 1:64 is negative then the titer is reported as less than this.

The test comes with this sample interpretation note:

Rickettsia rickettsii (Rocky Mtn. Spotted Fever) Ab, IgG:

  • Less than 1:64: Negative – No significant level of Rickettsia rickettsii IgG Antibody detected.
  • 1:64 – 1:128: Low Positive – Presence of Rickettsia rickettsii IgG Antibody detected
  • 1:256 or greater: Positive – Presence of Rickettsia rickettsii IgG Antibody, suggestive of recent or current infection.

So, how would you represent this one in the various HL7 specifications?

String Integer Structured
V2 OBX||ST|{test}||<1:64 {can’t be done} OBX||SN|{test}||<^1^:^64
CDA <value xsi:type=”ST”> &lt;1:64 </value>  {can’t be done} <value xsi:type=”IVL_RTO_INT_INT”> <high> <numerator value=”1”/> <denominator value=”64”> </high> </value>
FHIR “valueString “ : “<1:64” {can’t be done} “valueRatio”: { “numerator” : { “comparator” : “<”, “value” : “1” }, “denominator” : { “value” : “64” } }

This table shows how the stuctured/ratio form is better than the simple numeric – but there’s a problem: the CDA example, though legal in general v3, is illegal in CDA because CDA documents are required to be valid against the CDA schema, and IVL_RTO_INT_INT was not generated into the CDA schema. I guess that means that the CDA form will have to be the string form?

 

 

2 Comments

  1. Nick Radov says:

    Are you certain the first example for CDA Integer is correct? For an INT I think the value element should have a value attribute, not text content.

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