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Case Studies in Clinical Hemostasis Case Studies in ... - Pathology

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<strong>Case</strong> <strong>Studies</strong><br />

<strong>in</strong><br />

Cl<strong>in</strong>ical<br />

<strong>Hemostasis</strong><br />

<strong>Case</strong> #3<br />

The <strong>Case</strong> of the 3 Year-<br />

Old Child with Tonsillitis<br />

and an Elevated aPTT


Patient L.S.<br />

! Child with history of tonsillitis<br />

! Recurrent abdom<strong>in</strong>al distress and<br />

vomit<strong>in</strong>g<br />

! Normal birth and development, no<br />

other medical problems<br />

! No personal history of bleed<strong>in</strong>g or<br />

bruis<strong>in</strong>g<br />

! No family history of bleed<strong>in</strong>g disorder<br />

! Abnormal preoperative aPTT (34 sec)<br />

and bleed<strong>in</strong>g time (14.5 m<strong>in</strong>)<br />

! Referred to pediatric hematologist


Patient L.S.<br />

! What is the bleed<strong>in</strong>g time? How is it<br />

performed? How could the discrepant<br />

bleed<strong>in</strong>g time results be expla<strong>in</strong>ed?<br />

! What are common causes for an elevated<br />

aPTT?<br />

! What further laboratory studies should be<br />

performed?<br />

! What is the cause of the elevated aPTT <strong>in</strong><br />

L.S.?<br />

! Should the tonsillectomy be performed?<br />

What further therapy is <strong>in</strong>dicated?


The Bleed<strong>in</strong>g<br />

Time -<br />

Pot of Gold At<br />

The<br />

End Of The<br />

Ra<strong>in</strong>bow ?


Bleed<strong>in</strong>g Time<br />

❝ The time between the<br />

<strong>in</strong>fliction of a small<br />

<strong>in</strong>cision and the moment<br />

bleed<strong>in</strong>g stops ! ❞<br />

O’Brien, J.R.<br />

Am. J. Cl<strong>in</strong>. Pathol.<br />

4:272-285, 1951


What Determ<strong>in</strong>es The<br />

Bleed<strong>in</strong>g Time ?<br />

In vivo test of hemostatic function<br />

! Platelet function<br />

! Von Willebrand’s factor<br />

! Endothelial function<br />

! Coagulation factors<br />

! Circulat<strong>in</strong>g cellular elements


Bleed<strong>in</strong>g Time Procedure<br />

! Clean site with alcohol<br />

! Take medication history<br />

! Inflate blood pressure cuff to 40 mm<br />

! Make <strong>in</strong>cision with template<br />

! Beg<strong>in</strong> stopwatch<br />

! Blot <strong>in</strong>cision at 30 second <strong>in</strong>tervals<br />

! Red ➜ P<strong>in</strong>k ➜ Straw ➜ Endpo<strong>in</strong>t<br />

! Report <strong>in</strong> m<strong>in</strong>utes up to 15 m<strong>in</strong>utes


Bleed<strong>in</strong>g Time<br />

Reference Range<br />

! 2.5 - 10 m<strong>in</strong> - Blood 34:204-<br />

215,1969<br />

! 2.3 - 7.0 m<strong>in</strong> - AJCP 70:406-<br />

408,1978<br />

! 2.5 - 6.5 m<strong>in</strong> - Pediatrics 66:951-<br />

955,1980


Variability Of BT<br />

! Location & direction of <strong>in</strong>cision<br />

! Size and depth of <strong>in</strong>cision<br />

! Sk<strong>in</strong> characteristics<br />

! Venous pressure<br />

! Preparation of site<br />

! Patient cooperation<br />

! Blott<strong>in</strong>g technique<br />

! Endpo<strong>in</strong>t variation


Effect Of Platelet Count On<br />

Bleed<strong>in</strong>g Time<br />

30<br />

Uremia<br />

Platelet Count (x 10 4 /µl)<br />

25<br />

20<br />

10<br />

5<br />

ASA<br />

von Willebrand's Disease<br />

..<br />

ITP<br />

Harker, L.A. and Slichter, S.J.<br />

NEJM 287:155, 1972<br />

0<br />

0<br />

10 20 30 40 > 60<br />

Bleed<strong>in</strong>g Time (M<strong>in</strong>.)


Cl<strong>in</strong>ical Applications<br />

Of Bleed<strong>in</strong>g Time<br />

! Diagnostic test for bleed<strong>in</strong>g<br />

disorders<br />

! Predict risk of perioperative<br />

hemorrhage<br />

! Therapeutic<br />

decision-mak<strong>in</strong>g<br />

for drugs and blood products


U.S. Bleed<strong>in</strong>g Times -<br />

1,000,000/Year<br />

~ $35,000,000/Year


The Bleed<strong>in</strong>g<br />

Time As A<br />

Diagnostic Tool<br />

In<br />

The Bleed<strong>in</strong>g<br />

Patient


Bleed<strong>in</strong>g Time As<br />

Diagnostic Tool<br />

! Nieuwenhuis, Akkerman, and Sixma. Blood<br />

70:620, 1987<br />

! Detailed evaluation of 145 patients with<br />

history of bleed<strong>in</strong>g disorder, prolonged<br />

bleed<strong>in</strong>g time, and normal platelet count<br />

von Willebrand’s<br />

Disease<br />

Abnormal<br />

Thromboxane<br />

Synthesis<br />

Platelet Storage<br />

Pool Disease<br />

Other<br />

Abnormalities


Use of the<br />

Bleed<strong>in</strong>g Time<br />

to<br />

Predict<br />

Perioperative<br />

Hemorrhage


Always Get A<br />

Bleed<strong>in</strong>g History<br />

Before A<br />

Procedure !!


Preoperative Coagulation<br />

Test<strong>in</strong>g<br />

! Rohrer, Michelotti, and Nahrwold. Ann. Surg.<br />

208, 554, 1988<br />

! Efficacy of screen<strong>in</strong>g tests compared to<br />

efficacy of tests <strong>in</strong>dicated by history and/or<br />

physical examiantion<br />

! 1119 tests (BT, PT, PTT, PC) <strong>in</strong> 282 patients<br />

! 514 screen<strong>in</strong>g tests <strong>in</strong> 282 patients, 4.1%<br />

abnormal, none cl<strong>in</strong>ically significant<br />

! 605 <strong>in</strong>dicated tests, 7.4% abnormal<br />

! 44% of PT and PTTs, 59% of PCs, and 38% of<br />

BTs could be safely elim<strong>in</strong>ated, sav<strong>in</strong>g<br />

$370,000/year


Bleed<strong>in</strong>g Time As A<br />

Preoperative Screen<strong>in</strong>g Test<br />

! Barber et al. Am. J. Med. 78:761, 1985<br />

! Reviewed 1,941 bleed<strong>in</strong>g times performed as<br />

part of rout<strong>in</strong>e preoperative screen dur<strong>in</strong>g a six-<br />

month period<br />

! Prolonged bleed<strong>in</strong>g times (> 10 m<strong>in</strong>.) found <strong>in</strong><br />

110 patients (5.6%)<br />

! Bleed<strong>in</strong>g risk factors identified <strong>in</strong> 83/110<br />

patients (75%)<br />

! Only 2/27 patients without risk factors severely<br />

prolonged bleed<strong>in</strong>g times (> 20 m<strong>in</strong>.)


Applications<br />

of Bleed<strong>in</strong>g<br />

Time In<br />

Plann<strong>in</strong>g Drug<br />

Therapy And<br />

The Use Of<br />

Blood<br />

Products


Bleed<strong>in</strong>g Time As A<br />

Therapeutic Guide<br />

! Post-operative cardiopulmonary bypass -<br />

Platelet dysfunction versus mechanical problem<br />

! VWD - Resposne to DDAVP<br />

! Bleed<strong>in</strong>g associated with medications affect<strong>in</strong>g<br />

platelet function<br />

! Bleed<strong>in</strong>g associated with uremia - Response to<br />

DDAVP, estrogens, cryoglobul<strong>in</strong>, or dialysis<br />

! Bleed<strong>in</strong>g <strong>in</strong> patients with acute alcohol<br />

<strong>in</strong>toxication


The Bleed<strong>in</strong>g Time -<br />

Neither Pariah Nor<br />

Panacea<br />

Douglas Triplett, M.D.


Patient L.S.<br />

Repeated <strong>Studies</strong><br />

600<br />

20<br />

50<br />

20<br />

THOU/uL<br />

500<br />

400<br />

300<br />

200<br />

100<br />

●<br />

Seconds<br />

15<br />

10<br />

5<br />

●<br />

Seconds<br />

45<br />

40<br />

35<br />

30<br />

25<br />

●<br />

M<strong>in</strong>utes<br />

15<br />

10<br />

5<br />

●<br />

0<br />

PLTS<br />

0<br />

PT<br />

20<br />

aPTT<br />

0<br />

Bleed<strong>in</strong>g Time


Contact<br />

Factors<br />

- Charged<br />

Surface<br />

Modern Concept<br />

of Coagulation<br />

XI XI<br />

XIa XIa<br />

VII<br />

IX IX<br />

IXa IXa<br />

Tissue<br />

Factor<br />

Injured<br />

Tissue<br />

VIII<br />

VII<br />

XX<br />

Xa Xa<br />

V<br />

Prothromb<strong>in</strong><br />

Thromb<strong>in</strong>


Causes of Elevated aPTT<br />

! Hepar<strong>in</strong> adm<strong>in</strong>istration<br />

! Factor deficiency<br />

II, V, VIII, IX, XI, XII<br />

! Hypofibr<strong>in</strong>ogenemia (< 100 mg/dL)<br />

! Specific <strong>in</strong>hibitors<br />

! Non-specific<br />

<strong>in</strong>hibitors<br />

! Antithrombotic substances (FDPs)<br />

! Dissem<strong>in</strong>ated <strong>in</strong>travascular coagulation<br />

! Vitam<strong>in</strong> K deficiency


aPTT Inhibitor Screen<br />

Normal Plasma<br />

Patient Plasma<br />

1:1<br />

+<br />

Incubate<br />

Factor Deficiency - PT Corrected<br />

Factor Inhibitor - PT Uncorrected<br />

Perform<br />

Prothromb<strong>in</strong><br />

Time


aPTT Inhibitor Screen<br />

Mixture<br />

Un<strong>in</strong>cubated<br />

INTR<br />

Incubated<br />

INTR<br />

Normal Plasma<br />

23.6 sec<br />

-<br />

24.7 sec<br />

-<br />

Patient Plasma<br />

36.4 sec<br />

-<br />

45.5 sec<br />

-<br />

1 Normal:1<br />

Patient<br />

28.5 sec<br />

CRCT<br />

35.6 sec<br />

NCRCT<br />

1 Normal:4<br />

Patient<br />

32.9 sec<br />

NCRCT<br />

44.8 sec<br />

NCRCT<br />

4 Normal: 1<br />

Patient<br />

26.0 sec<br />

CRCT<br />

34.0 sec<br />

CRCT


Non-Specific<br />

Coagulation Inhibitor<br />

! Common <strong>in</strong> children with recurrent<br />

URI treated with repeated courses of<br />

antibiotics<br />

! Rarely associated with cl<strong>in</strong>ical<br />

bleed<strong>in</strong>g<br />

! Usually resolve with time<br />

! Exclusion of lupus anticoagulant, vWD,<br />

and congenital factor deficiencies<br />

essential


<strong>Case</strong> <strong>Studies</strong><br />

<strong>in</strong><br />

Cl<strong>in</strong>ical<br />

<strong>Hemostasis</strong><br />

<strong>Case</strong> #3<br />

The End

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