Headache is a symptom of severe preeclampsia and occurs in about 75% of women with

eclampsia where it always precedes the seizure. Headache in preeclampsia-eclampsia can be

bitemporal, frontal, occipital, or diffuse with most women describing the pain as pulsating
although a feeling of pressure or sharp pain is described by some. A characteristic feature is
its progressive nature and failure to respond to over-thecounter (OTC) remedies. It can be
associated with visual changes such as blurred vision, scotomata, or bright flashing lights.
The pathophysiology is largely unknown, but two aetiologies are suggested: (1) marked
vasospasm in the cerebral vasculature in response to elevated systemic blood pressure
resulting in ischaemia and (2) vasoconstriction of cerebral vasculature followed by reflex
vasodilatation leading to overdistension, extravasation of fluid and cerebral oedema.
Normally cerebral autoregulation protects against sudden changes in blood pressure;
however, when systolic blood pressure exceeds 150mmHg, the autoregulation starts to fail
and hypertensive encephalopathy may develop.
Sakit kepala adalah gejala dari preeklamsia berat dan terjadi pada sekitar 75% wanita dengan
eklampsia sebelum terjadi kejang. Sakit kepala pada preeklampsia-eklampsia dapat berupa
nyeri bitemporal, frontal, oksipital, atau difus dengan kebanyakan wanita menggambarkan
nyeri sebagai berdenyut meskipun beberapa lainnya menggambarkan nyeri kepala seperti
tekanan atau nyeri yang tajam. Karakteristiknya adalah nyeri progresif dan kegagalan respon
terap obat-obat pereda nyeri biasa (OTC). Hal ini dapat dikaitkan dengan perubahan visual
seperti penglihatan kabur, skotomata, dan kilatan cahaya. patofisiologi sebagian besar tidak
diketahui, tapi dua etiologi yang disarankan: (1) Vasospasme di pembuluh darah otak dalam
menanggapi peningkatan tekanan darah sistemik mengakibatkan iskemia dan (2)
vasokonstriksi pembuluh darah otak diikuti oleh refleks vasodilatasi menyebabkan
overdistensi, ekstravasasi cairan dan edema serebral. autoregulasi normal otak melindungi
terhadap perubahan mendadak tekanan darah, nmun, ketika tekanan darah sistolik melebihi
150 mmHg, autoregulasi mulai gagal dan dapat terjadi ensefalopati hipertensi.
Abdominal or chest tenderness and upper right upper side pain (from liver distention)
liver capsule distension produce epigastric pain, often with progressive nausea and vomiting
and can lead to ruptur.
distensi kapsul hepar menyebabkan nyeri epigastrium, sering disertai mual progresif dan
muntah dan dapat menyebabkan ruptur hepatika.

The classic pathologic hepatic lesions associated with HELLP syndrome are periportal
necrosis, microthrombi, and large fibrin deposits in the sinusoids. Obstruction of the
circulation leads to swelling of the liver with tension of the Glisson capsule, causing
abdominal pain.6 The clinical appearance of HELLP syndrome is protean. Patients with
HELLP syndrome may have various symptoms, including general malaise, nausea, vomiting,
weight gain, edema, headache, visual impairment, and jaundice. However, acute epigastric
and right upper quadrant pain, called the epigastric sign of Chaussier, is present in 90% of
cases of HELLP syndrome.

Lesi hepatik patologis klasik terkait dengan sindrom HELLP adalah nekrosis periportal,
mikrotrombi, dan deposit fibrin besar di sinusoid. Obstruksi sirkulasi menyebabkan
pembengkakan hati dengan distensi kapsul Glisson, menyebabkan nyeri.
Endothelial dysfunction is responsible for the clinical signs observed in the mother, ie,
impairment of the hepatic endothelium contributing to onset of the HELLP (Hemolysis,
Elevated Liver enzymes and Low Platelet count) syndrome, impairment of the cerebral
endothelium inducing refractory neurological disorders, or even eclampsia. Depletion of
vascular endothelial growth factor in the podocytes makes the endotheliosis more able to
block the slit diaphragms in the basement membrane, adding to decreased glomerular
filtration and causing proteinuria. Finally, endothelial dysfunction promotes microangiopathic
hemolytic anemia, and vascular hyperpermeability associated with low serum albumin causes
edema, particularly in the lower limbs or lungs
disfungsi endotel bertanggung jawab untuk tanda-tanda klinis yang diamati pada ibu, yaitu,
kerusakan endotel hati berkontribusi terhadap timbulnya HELLP yang (Hemolisis, enzim
Peningkatan hati dan hitung Low Platelet) sindrom, gangguan endotel otak merangsang
gangguan saraf refrakter, atau bahkan eklampsia. Deplesi faktor pertumbuhan endotel
vaskular di podocytes membuat endotheliosis lebih mampu memblokir celah diafragma di
membran basal, menyebabkan penurunan filtrasi glomerulus dan menyebabkan proteinuria.
Akhirnya, disfungsi endotel menyebabkan mikroangiopati anemia hemolitik, dan
hyperpermeability vaskular yang terkait dengan albumin serum yang rendah menyebabkan
edema, khususnya di tungkai bawah atau paru-paru

Thrombocytopenia occurs commonly during pregnancy, and may result from diverse
etiologies.
Thrombocytopenia (platelet deficiency) affects approximately eight percent of all
pregnancies. While about 30 percent of those cases are caused by conditions such as
autoimmune responses (e.g. lupus, abnormal destruction of platelets), infections, preeclampsia or HELLP syndrome, the remaining 70 percent fall under the category of nonpathological gestational thrombocytopenia,

Normal pregnancy is associated with a physiologic fall in the platelet count that is
characterized by a leftward shift in the platelet count distribution (Figure 1).2 The reason for
this decline is unknown, although it has been speculated that these changes may reflect
dilution, decreased platelet production, or increased platelet turnover during pregnancy
Generally, these individuals have mild thrombocytopenia that first
becomes apparent in the mid-second to third trimester of pregnancy.
Although there is no well-established minimum value for the

platelet count in gestational thrombocytopenia, most experts consider

this diagnosi

Penyebab trombositopenia dalam kehamilan bisa berupa tromositopenia saja (Isolated

thrombocytopenia) dan trombositopenia yang berkaitan dengan kelainan sistemik. Isolated
thrombocytopenia yaitu gestasional trombositopenia terjadi pada 70-80% wanita hamil,
trombositopenia yang berkaitan dengan kelainan sistemik diantaranya preeclampsia berat
(15-20%), Sindrom HELLP (<1%), dan AFLP (acute fatty liver of pregnancy) (<1%).
In recent years, several studies have provided insight into the pathogenesis of preeclampsia.
Although the clinicalmanifestations of preeclampsia usually do not appear until the late
second or third trimester, the pathologic processes underlying this syndrome reflect
inadequate placentation early in pregnancy. Placentation, the process by which fetal
trophoblast cells invade the maternal decidua and remodel the maternal uterine spiral
arteries, is necessary to ensure an adequate placental blood supply. In preeclampsia, both the
depth of trophoblast invasion and the extent of remodeling of the spiral arteries are reduced
(Figure 2); this may reflect deficiencies in trophoblast function, including failure of
trophoblast cells to alter their pattern of integrin expression toward an endothelial phenotype
and deficient protease activity, among others. Insufficient placentation results in progressive
ischemia of the fetoplacental unit as pregnancy advances, and fetal growth and oxygen
requirements increase.

Although deficient trophoblast invasion as a critical component of preeclampsia was

recognized many years ago, the mechanisms by which uteroplacental hypoxia induce the
systemic manifestations of preeclampsia have only more recently begun to be unraveled.
Recent studies have demonstrated that increased plasma levels of soluble vascular endothelial
cell growth factor (VEGF) receptor type 1 (sFlt1),as well as endoglin, an endothelial cellderived member of the tumor growth factor- (TGF-) receptor family, are present in patients

destined to develop preeclampsia as early as the late first trimester. Increased levels of sFlt1
and endoglin mRNA are present in preeclamptic placentae, suggesting this is the source of
these proteins. sFlt1 binds and neutralizes VEGF and placental growth factor (PLGF),
another important VEGF family member whose levels normally increase during pregnancy,
whereas endoglin blocks the binding of TGF- to endothelial cells.17 One outcome of these
actions is to decrease expression of endothelial nitric oxide (NO) synthase leading to reduced
NO production and exacerbation of the hypertensive manifestations of preeclampsia.
Functional deficiency of VEGF/PLGF also results in endothelial dysfunction, particularly
that of the glomerular endothelium, leading to the characteristic endothelial swelling and
glomerular endotheliosis lesions of preeclampsia and the development of a thrombotic
microangiopathy.
Studi terbaru menunjukkan bahwa peningkatan kadar plasma reseptor faktor pertumbuhan sel
endotel vaskular (VEGF) tipe 1 (sFlt1), serta Endoglin, sel endotel yang merupakan turunan
dari reseptor tumor growth factor (TGF-), pada pasien akan mengembangkan preeklamsia
dini pada akhir trimester pertama. Peningkatan kadar sFlt1 dan mRNA Endoglin ditemukan
pada plasenta preeklampsia, yang merupakan sumber protein. Reseptor sFlt1 mengikat dan
menetralisir VEGF dan faktor pertumbuhan plasenta (PLGF), anggota keluarga VEGF
penting yang lain, yang kadar normal meningkat selama kehamilan, sedangkan Endoglin
memblok pengikatan TGF pada sel endotel. Salah satu hasil dari aksi ini adalah penurunan
sintesis ekspresi nitric oxide (NO) endotelial yang menyebabkan berkurangnya produksi NO
dan eksaserbasi manifestasi hipertensi preeklamsia. defisiensi fungsional VEGF / PLGF juga
menghasilkan disfungsi endotel, terutama endotelium glomerulus, yang menyebabkan
pembengkakan endotel dan lesi "glomerular endotheliosis" preeklampsia dan pengembangan
microangiopathy trombotik.