Deep Vein thrombosis

What an practicing Obstetrician should know on Thromboembolism??

Point 1:-DVT remains a leading cause of obstetric morbidity and mortality.

. Point 2:- It is the hypercoagulable nature of pregnancy is the prime cause: of DVT & PE . Point 3 The hypercoagulable nature of pregnancy It remains more common in the postpartum period than during pregnancy. It is now recognized that a significant portion of these thrombotic events occur as early as the first trimester, it is prudent to start treatment soon after the pregnancy is recognized and viability confirmed, and continue until 6 weeks post delivery.

 . Point 4 Why DVT is more common in Pregancy??  The increased prevalence is due to arterio of equilibrium or balance of procoagulant and anticoagulant factors in the circulation pendulm favoring  toward clot formation during pregnancy. Under normal circum­stances, the increased levels of clotting factors do not result in thrombus formation, but some clinical situations such as trauma or vascular injury may predispose toward lower extremity clotting. Point 5 :- Other risk factors for thrombosis during pregnancy include venous status, inactivity, obesity, prior thrombosis, antiphospholipid syndrome and thrombophilias such as factor V Leiden mutation.

It is estimated that the risk of venous thrombosis is approximately five times higher during pregnancy than in the non­pregnant state due to the hypercoagulable nature of pregnancy. While previously thought to be more prevalent in the third trimester, it is now recognized to occur at similar frequencies throughout pregnancy. Point: 6:-  Despite its risk, thromboembolism during pregnancy is a poorly studied area and significant controversy remains over the management of pregnant women at risk for this disorder. Pathophysiology-of thrombosis--Normal pregnancy is associated with an increase in the level or activity of many of the clotting factors in the blood. These increases provide a defense against hemorrhage after delivery, but they also contribute to thrombus formation. Once formed, portions of the clot can emblozie  to the pulmonary tree, with symptoms rang­ing from mild hypoxia to cardiovascular collapse. With mild to moderate symp & few signs

How to measure AFI

Amniotic fluid measurement.
Technique
• uterus is divided into four imaginary quadrants with linea nigra and umbilicus acting as the vertical and the horizontal axis respectively
• the deepest pocket devoid of umbilical cord and fetal parts is measured in the vertical dimension
• measurement of the four pockets is in centimeters
• sum of all the four quadrant measurements is AFI
• normal AFI values range from 5 to 25 cm

1.                  Amniotic fluid index

The deepest, unobstructed, vertical pocket of fluid is measured in each quadrant in centimeters. The four pocket measurements are then added to calculate the AFI.
Values
• AFI between 8-18 cm is considered normal; median AFI level is ~14 cm from week 20 to week 35, after which the amniotic fluid volume begins to reduce.
• AFI <5-6 cm is considered as oligohydramnios. ...
• AFI >20-24 cm is considered as polyhydramnios

2. Maximum vertical pocket method.

The deepest (maximal) vertical pocket (DVP) depth is considered a reliable method for assessing amniotic fluid volume on ultrasound , It is performed by assessing a pocket of maximal depth of amniotic fluid which is free of umbilical cord and fetal parts.
The usually accepted values are:
• <2 cm: indicative of oligohydramnios
• 2-8 cm: normal but should be taken in the context of subjective volume.
• >8 cm: indicative of polyhydramnios

3. Two diameter pocket method.

The two diameter pocket (TDP) method is an alternative method of assessing amniotic fluid volumes on ultrasound. However, it is not thought to be good predictor of adverse neonatal outcome .
Sonographic assessment
• TDP <15 cm2: indicative of oligohydramnios
• TDP 15 - 50 cm2: usually taken as normal
• TDP >50 cm2: indicative of polyhydramnios

Amniotic Fluid Volume assessment -What is ployhydramnios , Oligohydramnios

Determination  of amniotic Fluid  volume

As   originally  described by Phelan   and associates  in order to calculate the  AFI   the abdomen is arbitrarily  divided  into four quadrants   in which the  umbilicus divides the upper  and    lower  halves  and the linea  nigra   divides   the right  and left halves. With the patient   supine the linear  transducer  is placed along the maternal anterior   abdominal  wall and   held perpendicular  to the floor. The maximum  vertical  pocket  of fluid   ( usually  reported  in centimeters )   equals the sum of  largest single vertical pocket of fluid  that is  at least  1 cm  in width  obtained following  the same  criteria described here .

AFV  has been   shown to result in over diagnosis of low AFV  ( oligohydramnios ).  In a  study    by Magann and colleagues     the use of color   Doppler   inappropriately  diagnosed  21% of  women with   low AFV  who actually had normal   dye determined AFVs . In  addition  color Doppler  did not identify  any more  pregnancies  with true dye determined low AFVs compared  with traditional   gray  scale ultrasound imaging .

Oligohydramnios  (Low AFV   referred to as oligohydramnios )  has been defined  as any one of the following .1)  A total  volume less than 200 mL  or less  than 500 mL  a value  below the 5 th percentile  for gestational   age 2)  an SDP ( single deep pocket ) less than 2 cm 3) an AFI    less than  5cm,  or 4) a subjectively low AFV.

An increased  AFV ( referred to as polyhydramnios ) can be defined    as any  one of the  following : A) a total volume  greater  than 2000 mL a value above  the 95^th  or 97  percentiles for gestational age B)  an SDP (single deep pocket ) greater  than   or equal  to 8 cm  C) an  AFI  greater  than or equal to 24 cm or greater  than 25 cm or D) a subjectively increased  AFV,

Polyhydramnios :-The   incidence  of polyhydramnios  ( also  referred to as hydramnios ) ranges  from 0.2%  to 2.0%   . The degree of polyhydramnios  can be described using  the terms mild moderate and  severe . Mild  polyhydramnios has been   defined as an a)  AFI  of 25 to 30 cm  or b)  a DVP  of 8 cm   or greater. But   moderate   polyhydramnios as A)  an  AFI   of 30. 1 cm  to 35 cm or B) a DVP of   12 cm or greater  . However,   severe polyhydramnios  as an 1)  AFI  of 35.1  cm or greater  2) or a DVP of   16 cm  or greater.

Idiopathic polyhydramnios accounts for approximately 50%    to 60%  of cases. The remaining  cases typically fall into  one of the  following   categories :  congenital   anomalies and genetic     disorders ( 8-45% ) , maternal  diabetes (  5- 26% )  multiple  gestations ( 8-10% )  fetal anemia   (1-11%)  and other   ( e.g.  hydrops fetalis , Bartter syndrome and congenital  viral  infections )   The mechanism  by which   idiopathic polyhydramnios  develops is not known . Memembrane  bound  water channels called aquaporins may play   a role in the  development   of polyhydramnios    but the exact physiology  is not yet understood.

 Increasing   severity of polyhydramnios correlates with an increased risk  of perinatal  death and congenital abnormalities .. Up to  31%   of pregnancies with severe    polyhydramnios  (AFI >35 ) have   a major   congenital    anomaly. The most   common structural anomalies associated with polyhydramnios are central nervous system cardiac tor gastrointestinal malformations  . The  risk of fetal aneuploidy in these   fetuses found to have an anomaly by sonography is 10%  . In those fetuses without sonographic evidence  of an anomaly the risk of aneuploidy  is only 1%   . The most   common trisomy 21,  trisomy 18,    and trisomy 13,   although other chromosomal  abnormalities can also  occur . There is not a significant  difference in the reported risk  of fetal  aneuploidy with increasing severity of polyhydramnios.

The  proposed  mechanism of polyhydramnios associated with maternal diabetes  is related  to fetal  polyuria   due to increased osmotic dieresis as a result of fetal  hyperglycemia . Poorer   glucose control  has been  shown to correlated with higher  amniotic  glucose concentration and higher  AFI. There may   also be an increase  in fetal  urinary   output in macrocosmic  fetuses ( which   are often   seen in diabetic  pregnancies )  The incidence  of polyhydramnios   in mothers   with  progestational   diabetes  after   24 weeks gestational  age has been shown  to be 18.8%    . In the setting of gestational diabetes the   incidence of polyhydramnios ranges from 8%  to 20%  and is found  up to 30 times  more often   than in non diabetic  pregnancies.

Cardiopulmonary Postpartum

Most patients present soon after delivery especially in the first week postpartum. The symptoms are suggestive of heart failure, for example, orthopnea and paroxysmal nocturnal dyspnea. These symptoms are usually attributed to normal pregnancy and that is why a diagnosis of postpartum cardiomyopathy can be easily missed. Physical examination findings include tachycardia, elevated jugular venous pressure, bilateral pulmonary crackles due to pulmonary edema, third heart sound (S3) and displaced apical pulse. Severe cases may present with acute respiratory failure or cardiogenic shock and a need for close monitoring in the intensive care unit. 

Some of the most common risk factors for the development of postpartum cardiomyopathy are as follows:

·         Advanced maternal age (more cases reported in both extremes of age) 

·         High parity (71% of women diagnosed with PPCM had three or more prior pregnancies).  High gravidity

·         Twin pregnancy (more endemic in women with twin pregnancies)

·         Use of tocolytic therapy (greater than 4 weeks can cause silent ischemia).

·         African descent (more prevalent in the African population)

·         Poverty

·         Hypertension

·         Cocaine abuse

ECG may show non-specific changes like sinus tachycardia, interventricular delay and sometimes, LBBB pattern.

Echocardiography suffices to differentiate it from other causes and usually shows left ventricle dilatation of variable degrees, left ventricle systolic dysfunction, right ventricular and bi-atrial enlargement, mitral and tricuspid regurgitation, and pulmonary hypertension.. Echocardiography criteria to diagnose PPCM includes ejection fraction less than 45%, end-diastolic diameter greater than 2.7 cm/m2 and/or M-mode fractional shortening less than 30%.

Cardiac MRI can also be used to diagnose when an accurate estimation of the ejection fraction (EF) is required.

Treatment / Management

Treatment is usually supportive and directed toward the management of the heart failure symptoms. Standard heart failure therapy is used to optimize the patient's volume status. Beta-blockers and ACEIs are the most commonly used drugs and have shown to lower the mortality

 However, an ACEI is contraindicated in pregnant patients. Diuretics are often used to ease symptoms related to heart failure. Novel anti-heart failure medications, such as sacubitril/valsartan have been reported to improve heart failure symptoms in pregnancy-related cardiomyopathies.

Recent data suggest that an increase in oxidative stress during the peripartum period increases the formation of abnormal 16-kDa prolactin which induces toxic effects on cardiac myocyte. Bromocriptine, a dopamine receptor agonist with prolactin-blocking properties, decreases the effect of 16-kDa prolactin on cardiac myocyte and has been associated with better outcomes in small studies. Cardiac resynchronization therapy has also shown to improve ejection fraction and outcomes when medical therapy alone is ineffective. Prognosis

·         Postpartum cardiomyopathy, also known as peripartum cardiomyopathy (PPCM), is defined as new onset of heart failure between the last month of pregnancy and 5 months post delivery with no determinable cause. First described in a case series in 1937. Postpartum cardiomyopathy is a rare cause of heart failure. Bottom of Form

Postpartum Cardiomyopathy

AcK:--Ateeq Mubarik; Arshad Muhammad Iqbal.

Circadian rhythm affects Pit releases Coticosteroids & PRL post Pituitary hormones

A glimpse on Pituitary gland & its hormones in reproduction:  We all owe to FSH & LH, PRL, TSH, Growth hormone, PRL, Corticosteroids The Ant Pit P is a gland distinct from the brain. The posterior pituitary (PP) is actually an extension of the brain - so PP secretions are Neurohormonal.

AP hormones are glandular hormones (not Neurohormonal). The hypothalamus (in the brain) secretes hormones into

the hypothalamic-hypophyseal portal veins. Most species have a distinct breeding season - reproduction shuts down for both sexes during parts of the year in which resources are limited. Breeding is timed so that young are growing fastest when resources are most abundant. Within the breeding season, the endocrine control of reproduction in males and females is very different - males are continuously fertile, but females ovulate cyclically. Control of ovulation is complex. Could start the description at several places - arbitrarily, I'll begin with ovary and follicles, and work up from there.  Even before a female is born, her ovaries hold ova (eggs, female gametes). In animmature female, each egg is enclosed in a primary follicle (small, no membrane). Most eggs in an adult female are also in primary follicles. At any time, a small subset develop into secondary follicles (larger, surrounded by membrane). \

In each estrous cycle, large secondary follicles are recruited to become Graafian follicles. Mature, Graafian follicles have a fluid filled cavity (the antrum). The egg itself projects into this space, surrounded by granulosa cells, which primarily secrete estrogen. The projection into the antrum is called the cumulus oophorus. A 'ripe' follicle moves up to the surface of the ovary so that it bulges out, with the cumulus oophorus on the side away from the ovarian wall. A site (the stigma) develops on the outer surface, where the tissue changes so that the follicle can rupture. At ovulation, the follicle splits and the eggshoots out with the antral fluid. Many secondary and Graafian follicles regress without ovulating (called atresia). This is not well understood, but it is normal after ovulating, the follicle fills with blood and lymph. The blood clot is resorbed as luteinization occurs, and is replaced by granulosa cells that form a corpus luteum (CL,'dark body' plural = corpora lutea). These cells primarily secrete progesterone.  After a period (usually a few days to a few weeks, but longer in some species), the CL.regresses, progesterone secretion drops, and it converts to a non-functional corpus albicantia ('white body') made mostly of connective tissue - eventually becomes barely detectable scar on surface of ovary. Endocrine control of ovarian cycles: Follicular phase: prior to ovulation, cells in the follicle primarily secrete estrogen. Luteal phase: after ovulation, cells in the corpus luteum primarily secrete progesterone, but also secrete some estrogen.Some shorthand - most of the estrogen is estradiol - E2 Progesterone - P4.. Noted before that there are many follicles in ovary. After an ovulation, the CL's from that ovulation secrete P4. But other pre-ovulatory follicle are growing, and they secrete E2.Result - the ratio of E2/P4 varies through time.

•         E₂:P₄ increases as follicle grows

•         E₂:P₄ drops abruptly at ovulation

•         E2:P4 increases as CL's regress

Variation in E2:P4 ratio is important in understanding how endocrine feedback loops control ovulation.

Higher levels controlling folliculogenesis and ovulation. Hypothalamus controls anterior pituitary (AP), which controls ovary.

 (Diagram of loops: GnRH, gonadotropins (FSH and LH), ovarian steroids (estrogen and progesterone).

Sequence of events:

1.       Hypothalamus secretes Gonadotropin Releasing Hormone (GnRH).

2.       GnRH stimulates secretion of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) by the AP. (always a + effect).

3.       FSH stimulates growth of pre-ovulatory follicles(s).

4.       As follicles grow, they secrete estrogen in increasing amounts. Two endocrine steps here -

LH stimulates ovary (thecal cells, outside follicle) to secrete testosterone.

FSH stimulates conversion of androgen to estradiol (granulosa cells, in follicle).

5.       LH and FSH feedback negatively on the secretion of GnRH by the hypothalamus. This helps to terminate the stimulation of follicles to grow.

6.       Estrogen and progesterone normally feedback negatively on the hypothalamus and AP. But as E2:P4 ratio increases, the feedback becomes positive.

7.       Note that the follicle is growing with constant level of FSH. It is an increase in sensitivity of ovary to FSH that causes follicular growth, initially.

8.       As E2 increases (b/c ovary is growing) E2:P4 ratio increases and feedback of estrogen on hypothalamus and AP switches to positive feedback.

9.       Shift to positive feedback causes estrogen surge.

10.   Estrogen surge, with positive feedback, causes ovulatory pulse of LH.

11.   LH pulse causes ovulation.

12.   Follicle becomes CL and secretes much more P4 than previously (but also secretes estrogens).

13.   Drop in E2 causes LH to return to baseline. If non-conceptive, FSH also drops to baseline. Feedback of steroids on AP and hypothalamus switches back to negative. Inhibin, an ovarian peptide hormone, also contributes to negative feedback.

CL collapses to become (nonsecretory) corpus albicantia after a period that varies among species. Prostaglandins, especially PGF2a, contribute to regression of CL (luteolysis). PGF2a may have multiple sources, but uterine

N T scan

First Trimester Screening (Nuchal Translucency and Blood Test)

The first trimester screening is a safe, optional test for all pregnant women. It's a way of checking foetal risk of certain birth defects, such as Down syndrome, Edward's syndrome (trisomy 18), trisomy 13 and many other chromosomal abnormalities as well as heart problems.It comprises USG and some  blood tets called Double marker tets at 11-13.6 weeks. It is a statistical evaluation of risk

What the Test Does ?

The screening involves two steps. A blood test checks for levels of two substances -- pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin. A special ultrasound, called a nuchal translucency screening, measures your baby's nasal bone as well as the fluid at the back of your baby's neck. A high volume of fluid can be a sign of problems.

The combined result of the blood tests and the ultrasound gives you a sense of your baby's risk. However, it's not a diagnosis. Most women who have an abnormal first trimester screening go on to have healthy babies.

Whether one get this test is her choice(optional) . Some women want the test so they can prepare. Others don't. They may decide that knowing the results wouldn't change anything. Or they feel that the test could result in unnecessary stress and invasive testing. However knowing of possible risks would allow for increased monitoring during your pregnancy as well as giving you delivery options (special hospital, pediatric surgeon availability).

How the Test Is Done

The first trimester screen won't harm foetus. A technician will take a quick blood sample from

Her  arm or fingertip.

The nuchal translucency screening is a normal ultrasound. It will take between 20 to 40 minutes.

What to Know About Test Results

If your results are normal, your baby has a low risk of these birth defects. If they're abnormal, she will be suggested further tests to rule out problems. These could include ultrasounds or invasive procedures, like CVS or amniocentesis.

. Remember: This test can't diagnose birth defects. It only shows if she

 has a greater risk than average of having some chromosomal abnormalities .

Sometimes test results are combined with a second- trimester screening. In that case, one  may not get test results until her  second trimester. Or she may get the results, and then get combined results after the second test

Rise of hCG in abnormal & normal pregancy

For   any foetal   problem be it anatomic / genetic such abnormalities are usually but not always it is reflected   on NT changes . Why it happens is unclear. As gestation changes   - NT    varies as per CRL.    .If the risk calculation (statistical risk probability) is above 1: 50 then only CVS procedure for confirmation.

Risk stratification:  We always  are concerned about  probability of chromosomal abnormality in any foetus ? If mother has one child with  Down’s syndrome, than recurrent risk will be 2%. . The chromosome analysis can be done either by 1) cell culture( traditional karyotyping)  or by more recently FISH method ( Fluorescent  In situ Hybridization).. In FISH method  Fluorescent probe is used on the nuclei of amniocytes one signal means that the said nucleus is having monosomy ( Fluorescent probe), two signals means euploid nucleus and if some nuclei reveals three florescent signals it applies trisomy..

FISH:- Usually there are five DNA probes(probes with Fluoro Chrome)  are used like 1) LS-1--21,    2) CEP-18,    3)  LS-1-13 4 & 5 ) CEP- two Sex chromatins    , The cells which shows two different signals after FISH procedure means normal cells i. e diploid chromosome with no alteration in number or decrease in number.&    5) Usually five chromosomes are  studied in nuclei of amniocytes .like 21, 13, 18 and two sex chromosomes. This tets of FISH may occasionally exhibit trisomy or monosomy.

Normally NT steadily increase    for the period foetal CRL from 44 mm  to 85 mm .What is normal NT(subcutaneous fluid collection behind the nape of the neck??  The fluid thickness is  for  a  CRL of 45 mm (  means 11 weeks ) will be  1.9 mm  in 85 percentile   and 50 percentile NT  will be   & NT  will  in 85 mm ( CRL at 13.6 ) but it will be 2.8 mm in 95 percentile

The nuchal translucency has to be differentiated from with cystic hygroma   which are two   dilated   Inguinal    lymphatic    sac or Tr   scar   it   the level of neck  which  is septate   for NT

Medical    geneticist > > 20 mm . Better cordo – P/M, H/P

High  res   scan – no   foetal  anatomical defect   ( cardiac   defect  then go for CVS

The NT is only reliable   from   45  - 84 mm  caliper     of  USG   should be  able   to read upto 0.1 mm.

 Sonoembryology:_---A) UPT will be +   13 day after  ovulation dose (trigger)   but B) in blood earlier   (RIA method  )  +   9 days after  ovulation .Therefore estimation  hCG   5 days after   test ovulation     done of hcg . Average  of 3  CRL measurements sac ( GDS)

Menstrual  week

4^th  M . Week = 2 mm sac

5thM. Week =  5mm  sac

6^th  M. week = 10 mm sac

7^th   M. week = 20 mm sac

8 th  M. week = 25mm sac

Vaginally USG:--  sac is visible  when   serum beta HCG  is  > 1500 to  1000 . But in abd USG(TAS) sac is visible when hCG is  > 3000. But usually at 5^th Weeks = SAC is visible almost always. By the end of 6th   weeks = Y. sac and cardiac    activity seen .At  8^th weeks  limb  buds are usually seen.

Biochemical pregancy??  :-  When  two  hcg values are greater than   10 IU/ lit   then  at this juncture if sac is not visible  - then it is called “Biochemical     Pregnancy”. 

Average 5 days + possible even in first trimester     usg

Clinical preg = Sac visible

hCG  at missed   dose ?

At the time of missed period (expected day of cycle, hcg in blood  will be   100miu/ ml

16-23 day=  10-30 IU

24-30 days  =  30-100 IU

31-38 days  = 10,000 to 16000 IU

Day 35- day 45   =  200-4000 IU

2-3 mm   =12000-200,000 IU

12weeks =  10,000 IU

Second  Tri  = 24000 – 55000 IU

3^rd Trimester   6000-48000 IU

Viability  Scan :-

1)                 Blighted ovum  - GSD > 8mm but there is   no Y sac in the USG  . 2) Anembryonic   pregnancy.  GSD > 16 mm , no foetal . p. signs  of failing IUP, )  bradycardia in   relation     to CRL   , MSD  ,  CRL is  < 5mm   I e  oligomaniotic sac , Poor  sac growth profile   , large Y. sac > 5.6 mm prior to 10 weeks  / abnormal Y. sac   , disappearance  of CL

Normally   rise of beta hCG   is > 1.24 times   , > 1.53, times  , >1.88 times  & > 2.33 times    in 24 h , 48 h   , 72 h    & 96 hours   but in ectopic   there will be only 20%  rise of B hCG   . If no intra uterine preg is visible preg then possibilities are a) EP b) missed abortion c)   failing IUP or d) self   resolution of EP

Always   perform USG if  B hCG is above 1500   . If at such  beta HCG(  above 1500)   sac  is demonstrated at USG then  in all fairness it is =normal pregancy,   no sac either   medical   treatment  MTX  or better  RPT  b hCG   after 48  hours  prog is less than   10   . In abdominal USG  sac should  be visible  when HCG  level  will be increases  6500 IU/ lit or

In normal pregancy the rise of b hCG will be  > 55%  by 48 hours   & at least   > 88 % by 72 hours