Fertility NEWS LETTER

Ideal fertility : ICSI / IVF & Genetic Center India

Dear Colleges
Hello

This time we had a journal club meeting where we discussed “ Caesarean Hysterectomy associated with consumptive Coagulopathy”. In that lecture Dr.Ritu Nema , presented coagulation in detail and discussed about the various tests in coagulopathy. I picked some of these test from various sources and putting them together in this news letter.

Another topic is very controversial, that is what is normal and abnormal amniotic fluid volume ? Sinologists reports various comments regarding the amniotic volume and we have to interpret them clinically and some times it is difficult for the obstetricians to give any correct answer to the patient ,regarding the risk to her baby in-utero. I lifted this topic from Callen’s text book on USG in Ob Gy.
I feel you are enjoying the news letters as I get some good comments from various parts of India. I need your blessing to continue this in future too.

Bye

Sincerely yours
Dr. D’Pankar Banerji

1. Some tests in Coagulopathy

a. Prothrombin time :

Its formal name is INR( International normalized ratio).It measures Extrinsic pathway of coagulation.
If patient is suspected to have abnormal bleeding :Since the Prothrombin time (PT) evaluates the ability of blood to clot properly, it can be used to help diagnose bleeding. When used in this instance, it is often used in conjunction with the PTT (partial thromboplastin time) to evaluate the function of all coagulation factors. Occasionally, the test may be used to screen patients for any previously undetected bleeding problems prior to surgical procedures.

If patient is prone for thrombosis and needs an Oral Anticoagulants :The International Normalized Ratio (INR) is used to monitor the effectiveness of blood thinning drugs such as warfare The results of PT performed on a normal individual will vary depending on what type of analytical system it is performed on. This is due to the differences between different batches o manufacturer’s tissue factors used in the reagent to perform the test. The INR was devised to standardize the results. Each manufacturer assign an ISI value( international sensitivity index) for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares to an internationally standardized sample. The ISI is usually between 1.0 and 2.0. The INR ratio of a patient’s prothrombin time to a normal (control) sample, raised to the power of ISI value for a analytical system used .

Vol VII Issue 4april2009

INR= ( PT test/ PT normal) raised to power ISI

Anticoagulants maintain the INR at 2.0 to 2.5

b. Activated partial thromboplastin time( partial thromboplastin time):

It is part of investigation( along with PT) of bleeding or thrombotic episode, and to monitor unfractionated ( standard) heparin therapy ( not for low molecular weight heparin). It monitors the intrinsic system of coagulation
Prolonged PTT tests may be due to:

1. Pre-analytical problems. These may include:

Insufficient sample - there must be enough blood collected. The anticoagulant to blood ratio must be 9:1 in the collection tube.
o Patients with high hematocrit levels may have prolonged PTT's.
o Heparin contamination. This is the most common problem, especially when blood is collected from intravenous lines that are being kept “open” with heparin washes.

o Clotted blood samples - the clotting process uses up some of the factors.

2. Inherited or acquired factor deficiencies.

Some factor deficiencies cause bleeding while others, called contact factors, prolong the PTT in vitro but do not cause bleeding and have little clinical significance. Prolonged PTT's due to factor deficiencies usually “correct” after being mixed with pooled normal plasma. PTT may be prolonged in von Willebrand’s disease.

3. A nonspecific inhibitor such as the lupus anticoagulant (LA).

If the LA does prolong the PTT or LA sensitive PTT, it will not correct with normal plasma mixing, but it will usually correct if an excess of phospholipid is added to the sample.

4. A specific inhibitor.

Although these are relatively rare, these are antibodies that attack a particular factor. They may develop in someone with a bleeding disorder who is receiving factor replacements (such as Factor VIII, which is used to treat hemophilia A) or spontaneously as an auto antibody. The specific inhibitor will prolong the PTT and it will not correct with mixing.

5. Heparin anticoagulant therapy

(the target PTT is often about 1.5 to 2.5 times higher than a patient’s pretreatment level).

6. Warfarin (Coumadin) anticoagulation therapy.

The PTT is not used to monitor warfarin therapy, but it may be affected by it.

7. Prolonged PTT levels may also be seen with leukemia.

Interpretation of PT and PTT in patients with a bleeding syndrome

c. Activated Clotting time ( activated coagulation time) :

It is a bed side test for heparin activity in blood ,but does not replace partial thromboplastin time. The ACT is sometimes used, along with the prothrombin time (PT) to help determine whether a bleeding episode is due to excessive anticoagulation or to depletion of coagulation factors.

d. Thrombin time:

The thrombin time involves only the addition of bovine or human thrombin to platelet poor plasma. It, therefore, reflects the conversion of fibrinogen to fibrin but is also sensitive to the presence of inhibitors e.g. heparin.

Thrombin cleaves fibrinogen, releasing fibrinopeptide A (FpA) and fibrinopeptide B (FpB) from fibrinogen and converting fibrinogen into a fibrin clot. Human thrombin (or bovine thrombin) is added to platelet poor plasma at 37°C and the time taken for the formation of a fibrin clot recorded.

2. Assessment of Amniotic Fluid Volume

Assessment of amniotic fluid volume is very important and it has a major role in Fetal Biophysical profile estimation and Modified biophysical profile. Both these method help us to assess the fetal status esp.in IUGR cases.

Who is having poly hydromnios and who is with oligohydramnios is sometimes become a perplexing question. If sinologist writes that “ fluid appears to be less or more” in fetal scanning report ,then the obstetrician gets confused and it is very difficult to take decisions.

Although there is good agreement on the significance of extremes of amniotic fluid volume ,there is controversy over the methodology used to make the diagnosis of either too much or too little amniotic fluid. Fluid assessment has to be subjective as objective assessments are too stringent and often not related to gestational age.

Two points should be remembered when assessing amniotic fluid volume .
First, amniotic fluid volume is large compared with fetal volume at early stages of gestation and should not be misinterpreted as polyhydramnios. Conversely , in term patients the normal volume of amniotic fluid is quite small so that only small pockets may be seen.

Second, patients who are obese often appear to have less than normal volumes of amniotic fluid. This may be due in part to scattering of sound with artifactual echoes within the amniotic fuid.

For Oligohydramnios, there are two points.

One in most cases it will imply the likelihood of a fetal renal malformation or severe growth restrictions in the absence of ruptured membranes, this diagnosis should only made when there is essentially no amniotic fluid .
Second , obstetrician should get immediate alert, as there is association of severe diminution with fetal death.

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Figure 2 : First IVF triplets