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CHAPTER
Disseminated 4
Intravascular
Coagulopathy and
Thrombocytopenia
Complicating
Pregnancy
• Philip Samuels
39
40 Chapter 4
proteolytic enzyme release may trigger DIC and can occur and this results in a consumptive coagulopathy. In these
in events such as placental abruption. This critical clinical cases, the earliest laboratory sign of DIC is a significant fall
picture, in other words, can have many etiologies. One must in fibrinogen, which is being consumed as it is converted to
rapidly determine the etiology while initiating therapy. fibrin. It is important to note that the concentration of
clotable fibrinogen is usually greatly increased during a nor-
Etiology mal pregnancy. A concentration that may be “labeled” as
The most common obstetric causes of DIC are listed in normal by your laboratory may, indeed, be abnormally low
Table 4-1. The most common underlying cause of mild for a pregnant patient. Therefore, the clinician should not be
DIC encountered by the obstetrician is probably underes- lulled into a false sense of security when the fibrinogen con-
timation of blood loss at the time of delivery with inade- centration is normal. A low-normal fibrinogen concentra-
quate replacement by crystalloid or colloid. In these cases, tion may actually be a huge drop for the individual patient,
vasospasm occurs with resultant endothelial damage and representing early DIC. The clinician must rely on the
initiation of DIC. Also, in these instances, hypotension overall clinical picture, because a “baseline” fibrinogen
occurs which results in decreased tissue perfusion leading concentration is usually not available.
to local hypoxia and tissue acidosis, which can further Severe preeclampsia and HELLP (hemolysis, elevated
exacerbate DIC by causing tissue release of cytokines. By liver transaminases, low platelets) syndrome can result in
keeping the patient’s volume replete, DIC can often be DIC if delivery is not effected promptly. Often these patients
avoided, even in the presence of profound anemia. show isolated thrombocytopenia, which should not be con-
Following placental separation after a vaginal delivery, fused with DIC in the absence of clinical bleeding or other
fibrinogen is activated to become a fibrin mesh, which coagulation abnormalities. This isolated thrombocytopenia
covers the old placental site. This, along with uterine con- is due to increased platelet destruction by the reticuloen-
traction, prevents excessive blood loss in the immediate dothelial system or decreased platelet synthesis in the bone
postpartum period. The genesis of this fibrin mesh results marrow, and is not a consumptive coagulopathy. Clinical
in a 10% reduction in the concentration of clotable fib- DIC in these cases is uncommon, unless the preeclampsia/
rinogen following a normal vaginal delivery. Placental HELLP is prolonged. Laboratory evidence of subclinical
abruption is a similar situation gone awry. In severe cases, DIC, nevertheless, is common in preeclamptics.
the placenta partially detaches from the wall of the uterus There is a common misconception that a retained dead
and a retroplacental clot forms. As the clot expands, it con- fetus commonly results in DIC. This rarely occurs and
sumes coagulation factors, which continually breakdown usually takes several weeks to develop. With effective cer-
vical ripening agents, there is no reason to expectantly
manage the intrauterine demise for extended periods. If,
however, an unsuspected demise is discovered and it
TABLE 4-1. Causes of DIC
appears that the fetus expired some time previously, a
Common causes coagulation profile is indicated.
• Massive hemorrhage, especially with inadequate Sepsis, regardless of cause, can be associated with DIC.
fluid replacement with crystalloid or colloid Obviously, any infection should be treated aggressively
• Placental abruption with antibiotics. New medications such as drotrecogin alfa
• Severe preeclampsia/HELLP, not isolated thrombocy- can greatly reduce mortality and DIC in sepsis. It, how-
topenia ever, is associated with increased bleeding diathesis and
Rare causes should only be administered under the supervision of
• Sepsis someone experienced with its use. There is no experience,
• Acute fatty liver of pregnancy however, with the use of this medication in pregnancy.
• Amniotic fluid embolus
• Adult respiratory distress syndrome
Diagnosis of DIC
• Acute hemolytic transfusion reaction
• Autoimmune disease The presumptive diagnosis of DIC is usually made clini-
• Malignancies cally, with confirmation made through laboratory studies.
• Retained dead fetus Table 4-2 shows readily available diagnostic tests. Other
research-based tests are available, but are not readily accessible
D I S S E M I N AT E D I N T R AVA S C U L A R C O A G U L O PAT H Y A N D T H R O M B O C Y T O P E N I A C O M P L I C AT I N G P R E G N A N C Y 41
TABLE 4-4. Blood Component Therapy for DIC in most common reason for hematology consultation during
Pregnancy gestation. Before diagnosing thrombocytopenia, the obste-
Fresh frozen plasma (FFP) (volume = 250 cc)
trician must make certain that the patient does not have a
• Used to correct PT, aPTT, and fibrinogen. Usually use platelet clumping disorder, which can give a spurious
as 4 units initially and then use more as needed. impression of thrombocytopenia. In 3 per 1000 individu-
• Use for clinical hemorrhage, if INR ≥2 with bleed- als, platelets will clump in EDTA, the diluent in lavender-
ing, if aPTT prolonged with bleeding. topped tubes used to analyze complete blood counts (CBC).
• Each unit of FFP increases the circulatory fibrino- In this process, platelets clump together so that many
gen 5-10 mg/dL. platelets are counted as a single platelet in the automatic
Cryprecipitate (volume = 35-40 cc)
analyzers. Examination of a peripheral smear as well as
• Rich in fibrinogen and used to raise fibrinogen checking a platelet count in a blue-topped tube containing
utilizing less volume than fresh frozen plasma. citrate can distinguish this from true thrombocytopenia.
• Administer when fibrinogen <100 mg/dL or if clinical Those with a clumping disorder are not truly thrombocy-
hemorrhage and fibrinogen <150 mg/dL. topenic and are not at risk for bleeding. This evaluation is
• Each unit of cryoprecipitate increases the circulatory shown in Fig 4-1. The causes for thrombocytopenia
fibrinogen 5-10 mg/dL. encountered during pregnancy are listed in Table 4-5.
Platelets The most common cause for true thrombocytopenia
• Transfuse if maternal platelets <20,000/mm3 accompanying pregnancy is gestational thrombocytopenia.
whether or not clinical bleeding. This disorder occurs in about 3% of pregnancies and is
• Transfuse if maternal platelets <50,000/mm3 in more frequent than all other causes of thrombocytopenia
the presence of hemorrhage. combined. It is generally characterized by mild, progressive
• Each pack of pooled platelets increases the platelet thrombocytopenia detected incidentally on a routine CBC.
count by 7,000-10,000/mm3. In DIC, transfused Any invasive evaluation or treatment for gestational throm-
platelets are consumed rapidly. bocytopenia may lead to more misadventure for the patient
PRBCs than the disease itself. To make this diagnosis, the patient
• Increase oxygen carrying capacity (a primary must have no history of a bleeding diathesis outside of preg-
priority). nancy. In general the platelet count should be >50,000/mm3
• Transfuse rapidly to keep up with clinical bleeding, and there should be no evidence of platelet clumping. Fewer
and try to keep hematocrit ≥25%. than 1% of uncomplicated pregnant women have a platelet
• Follow electrolytes as hemolysis and RBC transfu- count less than 100,000/mm3. Therefore, the lower the
sion can lead to elevated serum potassium.
• Give one ampule of calcium after each 5 units of
PRBCs since the anticoagulant in the packed units
will chelate circulatory calcium. Platelets <150,000/mm3
blood loss or underestimate the volume of crystalloid/blood Repeat count in blue- Examine peripheral
topped (citrate) tube smear
components administered. It is crucial to keep meticulous
track of this. If the patient is not given enough volume, she Normal Depressed No
Clumping
could develop acute renal failure. Conversely, if an overabun- count count clumping
dance of fluid is administered, the patient can develop fluid
overload and pulmonary edema. Not Patient has Probably not
thrombocytopenic thrombocytopenia thrombocytopenic
therefore safe to assume that the predictive values of these TABLE 4-6. Classic Findings in Thrombotic
tests in predicting neonatal thrombocytopenia will also vary. Thrombocytopenic Purpuraaa
It is also important to understand that ITP can be the har-
• Microangiopathic, hemolytic anemiab
binger of lupus erythematosus or other autoimmune dis- • Thrombocytopeniab
eases. The physician should take an appropriate history and • Neurologic abnormalitiesb
look for physical signs that may cause suspicion for these • Confusion
disorders. • Headache
Most physicians feel that vaginal delivery is acceptable • Paresis
even in the case of an infant with an extremely low platelet • Visual hallucinations
count. Therefore, cordocentesis and scalp sampling for • Seizures
platelet count are not indicated in these patients. Nonethe- • Fever
less, I feel it is useful to know which patients are at risk of • Renal dysfunction
delivering a profoundly thrombocytopenic neonate.
a
The classic pentad is found in 40% of patients.
Therefore, I do look for circulating antiplatelet IgG in b
This triad is present in 75% of patients.
pregnant patients with true ITP. If present, I avoid opera-
tive vaginal delivery, and try to avoid scalp electrodes if
possible. Furthermore, I am reticent about allowing these
patients to have a prolonged second stage of labor. In any but intermittent and chronic relapsing forms do exist,
case of ITP, I notify the pediatric team so a neonatal though rarely. See Chap 15 for a more detailed discussion
platelet count can be obtained. on this disorder and differential diagnosis.
Thrombotic thrombocytopenic purpura (TTP) is a rare
disorder, but one that must be considered when a pregnant Treatment
patient’s platelet count is severely depressed. Clinical ramifi- When does ITP require therapy? Spontaneous bleeding
cations are severe, and the disease is life-threatening. Patho- usually does not occur until the platelet count falls to
logically, platelets aggregate, producing platelet thrombi that around 20,000/mm3, and surgical bleeding does not occur
occlude arterioles and capillaries. This can produce ischemia until the platelet count falls to about 50,000/mm3. Many
and infarction in any organ system. It frequently affects those hematologists, therefore, do not empirically treat a patient
systems most dependent on microcirculation such as the until the platelet count approaches 20,000/mm3 unless
brain and kidneys. The cause of TTP remains elusive, but there is clinical bleeding. There is a relatively new test that
probably includes the arachadonic acid/prostaglandin path- may help determine which patients are at high risk. The
way as well as plasminogen and its activators. platelet function analyzer can rapidly determine if platelets
TTP is a clinical diagnosis, and the disorder is character- are functional by seeing how long it takes for them to
ized by a pentad of findings (Table 4-6). The classic pentad aggregate when exposed to different stimuli.
of signs/symptoms occurs in only about 40% of patients, The commonly used modalities for treating ITP when it
whereas approximately 75% of patients experience the exacerbates during pregnancy are listed in Table 4-7. Gluco-
triad of microangiopathic hemolytic anemia, thrombocy- corticoid administration remains the initial line of therapy.
topenia, and neurologic changes. TTP (non-familial) may If rapid response is needed, intravenous methylprenisolone
be caused by autoantibodies against ADAMTS-13, a metal- is used. It has an advantage over hydrocortisone as it has
loprotease that is responsible for cleaving ultra-large von much less mineralocortoicoid effect. Usually 1.0 to 1.5
Willebrand multimers. When TTP occurs during preg- mg/kg total body weight of methylprednisolone is adminis-
nancy, it usually occurs antepartum, and possibly during tered daily in two or three divided doses. An initial response
the second trimester. It may be confused with HELLP is usually seen within 2 days, but in refractory cases, it may
(hemolysis, elevated liver transaminases, low platelets) syn- take as long as 10 days to see a maximum response. After
drome. The degree of microangiopathic anemia is more the anticipated response is obtained, the patient should be
severe in TTP and is usually readily evident on the periph- switched to oral prednisone and the dose should be tapered
eral smear. Occasionally a depressed antithrombin III level to keep the platelet count arbitrarily around 100,000/mm3.
will be seen in HELLP syndrome and aid in the distinction If it is not emergent, therapy can be initiated with oral
between the two disorders. TTP is usually nonrecurring, prednisone on an outpatient basis. The usual starting dose
D I S S E M I N AT E D I N T R AVA S C U L A R C O A G U L O PAT H Y A N D T H R O M B O C Y T O P E N I A C O M P L I C AT I N G P R E G N A N C Y 45
TABLE 4-7. Treatment Modalities for ITP During TABLE 4-8. Tips for Tapering Steroids
Pregnancy
Tapering must be individualized and patients must be
Glucocorticoids
observed for symptoms
• Intravenous
• Parameters that must be taken into account when
• Methylprednisolone 1.0-1.5 mg/kg daily in two or
tapering glucocorticoids in order to prevent adrenal
three divided doses
crisis
• Prednisone 1.0 mg/kg/d>
• Age
• Then taper
• Patients older than 40 must be weaned very slowly
Intravenous immunoglobulin • Duration of therapy
• 0.4-1.0 g/kg/d for 3-5 days • No tapering needed for <1 wk of therapy
• May be repeated • Rapid tapering if 1-2 wk of therapy
Splenectomy • Slow taper if >2 wk of therapy
• Best carried out in second trimester • Dosage of prednisone used
• Taper rapidly to 40 mg/d
Platelet transfusion • Taper from 40-20 mg/d over several days
• Reserved for severe active bleeding • Taper from 20 mg/d to none over an extended
• May cause more rapid platelet destruction period of 2-4 wk, especially if duration of therapy
• Each unit of platelets raising count about 7000- has been >2 wk
10,000/mm3
Platelet count
Platelet
≤20,000/mm3
count
or clinical
>20,000/mm3
bleeding
Fails to Platelet
respond count rises
Change to oral
Intravenous
prednisone, 1 mg/kg/d,
immunoglobulin
then taper to keep
0.4-1.0 g/kg/d
platelets approximately
for 3-5 days
100,000/mm3
Fails to Platelet
respond count rises
Repeat as
Splenectomy
necessary
Fails to Platelet
respond count rises
TABLE 4-9. Surgical Tips for Performing a Cesarean Delivery on a Patient with a Bleeding Diathesis
• Use a midline incision if there is clinically significant bleeding. Otherwise a Pfannenstiel incision is acceptable.
• Use electrocautery liberally, especially in opening the subcutaneous tissue.
• Close the uterus meticulously from the start. The more needle holes you put in the uterus, the more it will
bleed.
• Leave the bladder flap open to prevent hematoma formation that could later lead to abscess. Cauterize the edge
of the bladder flap if necessary.
• Close the peritoneum in order to prevent bleeding from the edges. This also prevents subfascial bleeding from fill-
ing the peritoneal cavity and allows placement of subfascial drains.
• If there is oozing, place subfascial drains and leave them in place until they stop draining.
• Use skin staples, even in Pfannenstiel incisions. This allows partial opening of the incision if a subcutaneous
hematoma or seroma forms.
• Place a pressure dressing over the incision and leave it in place until the danger of bleeding subsides.
D I S S E M I N AT E D I N T R AVA S C U L A R C O A G U L O PAT H Y A N D T H R O M B O C Y T O P E N I A C O M P L I C AT I N G P R E G N A N C Y 47
Methylprednisolone, 0.75
mg/kg IV q12 h
No
Continue therapy Continue therapy for Add additional
remission
for 5 days 3-4 wk therapy
Splenectomy Azathioprine
Complete
response
Vincristine, 1.4 mg/m2 IV Substitute
Follow platelet count (2 mg maximum) on day 1, cryosupernatant for fresh
and watch for relapse followed by 1 mg IV on frozen plasma in plasma
days 4 ,7, 10 exchange
FIGURE 4-4. Management of the gravida with TTP. Before adopting this approach, the treating
physician must be certain of the diagnosis. TTP is a clinical diagnosis and can mimic severe
preeclampsia. The criteria for diagnosing TTP are listed in Table 4-6.
Intensive plasma manipulation is the key for treating Glucocorticoids should be administered to all patients
TTP. Therapy usually entails a combination of plasma- with TTP immediately after diagnosis. The usual dose
pheresis and plasma exchange with platelet-poor fresh is 0.75 mg/kg of intravenous methylprednisolone every
frozen plasma (FFP, 3-4 L/d). Plasmapheresis removes 12 hours until the patient recovers. Then slow tapering
platelet-aggregating substances, and plasma infusion pro- should be performed.
vides some antiaggregating products, such as ADAMTS-13, If a patient does not begin to respond within 5 days of
which are deficient in the patient’s plasma. If exchange therapy, or if her condition deteriorates within the first
plasmapheresis is not readily available, infusion of FFP 3 days, other therapies should be considered including vin-
(30 mL/kg/d) can be used as a temporizing measure. If cristine, azathioprine, and splenectomy. In refractory
this is done, the treating physician must be careful to watch cases, cryosupernatant may be substituted for FFP in the
for signs of volume overload and administer diuretics if plasma exchange protocol. Treatment of the pregnant
necessary. If a patient responds to plasmapheresis, this pro- patient with TTP is outlined in Fig 4-4.
cedure should be continued for at least 5 days. In patients
who exhibit a partial response without clinical deteriora- SUGGESTED READING
tion, plasmapheresis and plasma exchange should be con- Aster RH. Gestational thrombocytopenia. A plea for conserva-
tinued for 3 to 4 wk to achieve complete remission. Also, tive management. N Engl J Med. 1990;323:264.
packed red blood cells (PRBCs) should be administered to Burrows RF, Kelton JG. Low fetal risks in pregnancies associ-
keep the hemoglobin at an acceptable concentration. The ated with idiopathic thrombocytopenic purpura. Am J Obstet
physician should also carefully monitor renal function. Gynecol. 1990;164:1147.
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