Interesting case conference - PowerPoint Presentation

Slide1

Interesting case conference

Xuan Wang

12/10/2015

Slide2

Case scenario

HPI:

62-year-old man with a history of HTN, HLD and diabetes admitted for acute cerebrovascular accident in the right MCA territory and found to be severely anemic (

Hgb

6.2 gm/

dL

)

. He was transferred to VUMC for further care. On the day that he was brought to VUMC, his family noticed that he was jaundiced. Patient did not have prior history of jaundice and denied changes in his urine, easy bruising, bleeding, rash, fever, chills, night sweats and lymphadenopathy.

PMH:

HTN, DM 2

Surgical history:

Hernia repair, left arm surgery following an accident

Social history:

Foreman at a Christian Center. Married with 2 daughters.

Medications:

Oral

hypoglycemics

, amlodipine 5 mg daily

Slide3

Case scenario

Pertinent labs upon arrival

WBC 9.1;

Hgb

6.7 gm/

dL

;

Hct

17%;

Plt

715

MCV 102

fL

; Reticulocyte count 9.4%

LDH 885 unit/L;

Haptoglobin

<8 mg/

dL

Total bilirubin 7.7 mg/

dL

; conjugated bilirubin 5.3 mg/

dL

Labs most consistent with

hemolytic anemia

Slide4

Case scenario

Due to unclear etiology of CVA and hemolytic anemia, additional testing was performedRPR: Reactive, 1:8 titerSPEP: Normal total proteinCold agglutinin workupDAT negative for IgG and positive for C3d (2+)Flow cytometry: Small population (5.6% of total cells) of Kappa restricted CD5-/CD10- B cell suggestive of marginal zone lymphoma or lymphoplasmacytic lymphoma.Body CT did not reveal any evidence of disease

Sc

I (I)

Cord (

i

)

4°C

1:64

1:8

RT

NT

NT

30°C

1:2

1:1

37°C

0

0

Slide5

Additional pending tests

Hematologic tests

JAK2 (V617F) Mutation Analysis

BCR/ABL

Mutation

Confirmatory syphilis tests:

FTA-ABS

(Fluorescent

treponemal

antibody absorption

)

MHA-TP (

Microhemagglutination

assay

)

Slide6

Blood Bank page

Given the patient’s reactive RPR and hemolytic anemia, Blood Bank was asked about performing a

Donath

-Landsteiner test for

patient

How is syphilis and

Donath

-Landsteiner test related?

What is appropriateness of performing the D-L test?

And how would test result influence clinical management?

Slide7

Syphilis

Chronic

infection caused by the bacterium 

Treponema

pallidum

Primary syphilis

–

chancre

at the site of

inoculation

Secondary syphilis

– systemic disease in 25% of untreated individuals

A rash (most characteristic finding)

Fever

Headache

Malaise

Anorexia

Diffuse lymphadenopathy

Tertiary (late) syphilis

– symptomatic

manifestations of the disease involving the

CNS,

the cardiovascular system, or the skin and subcutaneous tissues (

gummas

).

 

CNS syphilis may occur early

as one year after initial infection to 25 years

later

CNS manifestations: meningitis (

infectious

arteritis), cranial neuropathy

 

(optic

, facial, or auditory

nerves), general paresis,

tabes

dorsalis

Slide8

Syphilis - Diagnosis

Screening tests (

nontreponemal

)

Venereal Disease Research Laboratory (VDRL)

Rapid Plasma

Reagin

(RPR)

Confirmatory tests (

treponemal

)

Fluorescent

treponemal

antibody absorption (

FTA-ABS)

Microhemagglutination

test for antibodies to 

T.

pallidum

 (

MHA-TP)

T

.

pallidum

 particle agglutination assay (

TP-PA)

T

.

pallidum

 enzyme immunoassay (TP-EIA)

Slide9

Donath-Landsteiner antibody

Seen in paroxysmal cold hemoglobinuria (PCH)The term PCH was named for a recurrent complication in late-stage or congenital syphilis: sudden attacks of constitutional symptoms and hemoglobinuria precipitated by exposure to cold temperatures With the advent of antibiotics and the almost complete eradication of late syphilis, this chronic relapsing form of PCH is now extremely rarePCH now tends to be an acute non-recurring illness affecting the pediatric population.

Slide10

What is a D-L antibody?

IgG antibody with anti-P specificity that sensitizes RBCs at cold temperatures (<20°C) by fixing the early components of complement

The antibody then dissociates at warmer temperatures

Complement activation is maximal

at

37°C and proceeds to completion to produce hemolysis

Hence, D-L Ab is called a

biphasic

hemolysin

Slide11

History

1904 – Julius

Donath

and Karl Landsteiner were the first to attribute the temperature-dependent hemolysis in PCH to a cold-reacting

autohemolysin

and warm-reacting lytic factor

(Eder

, 2005)

Early 1900s, 90% of cases were secondary to syphilis, particularly congenital syphilis

(Heddle, 1989;

Gottsche

et al

, 1990)

Now seen almost exclusively in children following infection

30-40% of AIHA in young children

0.4/100,000 in children <5

yrs

(

Sokol

et al

, 1999)

Slight male predominance

Rare examples of D-L antibodies in adults with other immunologic disorders (

lymphoproliferative

, collagen disease, delayed hemolytic transfusion

rxn

)

Slide12

Eder

AF. Immunohematology. 2005.

Slide13

Pathogenesis

PCH has been associated with a wide range of infectious agents (bacterial and viral) and rarely, recent immunization

Eder AF.

Immunohematology.

2005.

Slide14

Pathogenesis II

Inciting stimulus for autoantibody formation is unknown but a few hypotheses:

P antigen may be altered by an infectious agent so as to stimulate

autoAb

formation

Molecular mimicry: Infectious agent may possess antigens similar to P antigen and the resultant antibodies will cross-react

Increased production of autoantibodies due to increased lymphocyte activation

Slide15

Clinical Presentation of PCH

Typical presentation: Young child with recent history of URI or other acute illness presents with red-brown urine, often accompanied by pallor, jaundice and fever

Slide16

Laboratory findings of PCH

Intravascular hemolytic anemiaDecreased complement components ReticulocytopeniaObserved early but usually briefErythrophagocytosis20% of acute PCH

Blood,

2011

Slide17

How is it performed?

A tubes: Incubated at 0°C for 30 mins and 37°C for 60 minsB tubes: Incubated at 0°C for 90 minsC tubes: Incubated at 37°C for 90 mins

T

ubes 1:

Patient serum only

Tubes 2:

Patient serum and fresh donor serum

T

ubes 3:

Fresh donor serum only

Slide18

Donath-Landsteiner test

False positive: If patient has cold autoantibody with broad thermal amplitude

False negatives

Low

antibody

titer

Inhibition

of the

antibody by neutralizing carbohydrate antigens present in fresh donor serum

Transience of autoantibody (may be only present in plasma for a few days)

Slide19

Differential diagnosis

Cold agglutinin syndrome

Typically IgM with specificity of anti-I or

anti-

i

Thermal amplitude >30°C and titer>1:500

Slide20

Management

Acute DL-HA usually resolves spontaneously

and completely within several weeks

Usually does not recur

Treatment is supportive

Patient should be kept warm

Transfusion if severe

anemia; use blood warmer

Steroids have been given in cases, but effectiveness of therapy may be difficult to evaluate

In rare cases of life-threatening anemia, plasmapheresis has been used to acutely remove IgG antibodies

Slide21

Back to the patient

The Blood Bank team convinced the clinical team of the low utility of performing the D-L test.

Slide22

Patient follow-up

DatePCV   Plt-Ct   RBC/WB   12/09/15 05:10   35  539  --  12/08/15 06:10   36  536  --  12/07/15 07:06   30  502  --  12/06/15 04:00   29  530  --  12/05/15 02:45   27  557  --  12/04/15 03:30   26  628  --  12/03/15 03:30   29  506  --  12/02/15 15:25   24  663  --  12/02/15 11:38   --  --  RBC Transfd  12/02/15 07:36   --  --  RBC Transfd  

Date

Hgb   PCV   12/09/15 05:10   11.0  35  12/08/15 06:10   11.6  36  12/07/15 07:06   10.3  30  12/06/15 04:00   9.9  29  

DateTBil   LDH   CBil   12/09/15 05:10   1.9  --  --  12/08/15 06:10   2.0  390  --  12/05/15 02:45   2.2  681  1.5  12/04/15 03:30   2.6  640  1.8  

Patient was started on high dose steroids on 12/3

PCV improved after transfusions (15% prior to pRBCs) and steroids

MHA-TP negative. FTA-ABS pending

Hematologic molecular tests negative.

Discharged

on 12/8 to rehab with plan to wean steroid dose 5-10 mg every seven

days

Slide23

References

Eder AF

.

Review: acute Donath-Landsteiner hemolytic anemia

. Immunohematology

. 2005;21(2):56-62

.

Rausen

AR,

LeVine

R, Hsu TC,

Rosenfield

RE

.

Compatible

transfusion therapy for paroxysmal cold

hemoglobinuria. Pediatrics

. 1975 Feb;55(2):275-8

.

Sokol

RH, Hewitt S, Stamps BK, et al. Autoimmune

haemolysis

in childhood and adolescence. 

Acta

Haematol

. 1984;72:245–257

.

Sokol

RJ, Booker DJ, Stamps R

.

Erythropoiesis: Paroxysmal Cold

Haemoglobinuria

: A

Clinico

-Pathological Study of Patients with a Positive

Donath

-Landsteiner

Test. Hematology

. 1999;4(2):137-164.

Heddle

NM. Acute paroxysmal cold hemoglobinuria. 

Transfus

Med Rev

. 1989;3:219–229.