HELLP syndrome

HELLP syndrome is a life-threatening obstetric complication usually considered to be a variant or complication of pre-eclampsia.[1] Both

conditions usually occur during the later stages of pregnancy, or sometimes after childbirth. "HELLP" is an abbreviation of the three main features

of the syndrome:[2]

H emolysis

Elevated L iver enzymes

L ow  P latelet count

Contents

  [hide] 

1 Signs and symptoms

2 Pathophysiology

3 Diagnosis and classification

4 Treatment

5 Prognosis

6 Epidemiology

7 History

8 See also

9 References

[edit]Signs and symptoms

HELLP usually begins during the third trimester; rarely cases have been reported as early as 23 weeks gestation. Often, a patient who develops

HELLP syndrome has already been followed up for pregnancy-induced hypertension (gestational hypertension), or is suspected to develop pre-

eclampsia (high blood pressure and proteinuria). Up to 8% of all cases present after delivery.

Women with HELLP syndrome often "do not look very sick."[3] Early symptoms can include:

In 90% of cases, either epigastric pain described as "heartburn" or right upper quadrant pain.[3][4]

In 90% of cases, malaise.[4]

In 50% of cases, nausea or vomiting.[4]

There can be gradual but marked onset of headaches (30%), blurred vision, and paresthesia (tingling in the extremities). Edema may occur but its

absence does not exclude HELLP syndrome. Arterial hypertensionis a diagnostic requirement, but may be mild. Rupture of the liver capsule and a

resultant hematoma may occur. If the patient has a seizure or coma, the condition has progressed into full-blown eclampsia.

Disseminated intravascular coagulation is also seen in about 20% of all women with HELLP syndrome,[5] and in 84% when HELLP is complicated

by acute renal failure.[6] Pulmonary edema is found in 6% of all women with HELLP syndrome,[5] and in 44% when HELLP is complicated by acute

renal failure.[6]

Patients who present with symptoms of HELLP can be misdiagnosed in the early stages, increasing the risk of liver failure and morbidity.[7] Rarely,

post caesarean patients may present in shock condition mimicking either pulmonary embolism or reactionary haemorrhage.

[edit]Pathophysiology

The exact cause of HELLP is unknown, but general activation of the coagulation cascade is considered the main underlying problem. Fibrin forms

crosslinked networks in the small blood vessels. This leads to amicroangiopathic hemolytic anemia: the mesh causes destruction of red blood

cells as if they were being forced through a strainer. Additionally, platelets are consumed. As the liver appears to be the main site of this process,

downstream liver cells suffer ischemia, leading to periportal necrosis. Other organs can be similarly affected. HELLP syndrome leads to a variant

form of disseminated intravascular coagulation (DIC), leading to paradoxical bleeding, which can make emergency surgery a serious challenge.

[edit]Diagnosis and classification

HELLP syndrome can be difficult to diagnose due to the variability of symptoms among patients (frequently patients have no symptoms other than

general abdominal pain), and early diagnosis is key in reducing morbidity. If not treated in a timely manner, a mother can become critically ill or die

due to liver rupture/hemorrhaging or cerebral edema.

In a patient with possible HELLP syndrome, a batch of blood tests is performed: a full blood count, liver enzymes, renal

function and electrolytes and coagulation studies. Often, fibrin degradation products (FDPs) are determined, which can be elevated. Lactate

dehydrogenase is a marker of hemolysis and is elevated (>600 U/liter). Proteinuria is present but can be mild.

In one 1995 study, a positive D-dimer test in the presence of preeclampsia was reported to be predictive of patients who will develop HELLP

syndrome.[7][8]

The diagnostic criteria for and subtypes of HELLP vary across studies, which "makes comparison of published data difficult."[1] The classifications

include:

Criteria developed at the University of Tennessee:[4][9]

HELLP is characterized by hemolysis on peripheral blood smear with serum lactate dehydrogenase >600 IU/L; serum aspartate

aminotransferase >70 IU/L; and platelet count <100,000/μL.

Partial HELLP syndrome is characterized by 1-2 features of HELLP.

Criteria developed at the University of Mississippi, as of 1999:[10]

"The diagnosis of HELLP syndrome required the presence of thrombocytopenia (perinatal platelet nadir ≤150,000 cells/μL), evidence of

hepatic dysfunction (increased aspartate aminotransferase level of ≥40 IU/L, increased alanine aminotransferase level of ≥40 IU/L, or

both, with increased lactate dehydrogenase [LDH] level of ≥600 IU/L), and evidence of hemolysis (increased LDH level, progressive

anemia)...."

"Class 1 HELLP syndrome featured severe thrombocytopenia with a platelet nadir of ≤50,000 cells/μL, class 2 HELLP syndrome featured

moderate thrombocytopenia with a platelet nadir between >50,000 and ≤100,000 cells/μL, and class 3 HELLP syndrome featured mild

thrombocytopenia with a platelet nadir between >100,000 and ≤150,000 cells/μL."

Criteria developed at the University of Mississippi, as of 2006: "For a patient to merit a diagnosis of HELLP syndrome, class 1 requires severe

thrombocytopenia (platelets ≤50,000/μL), evidence of hepatic dysfunction (AST [aspartate aminotransferase] and/or ALT [alanine

aminotransferase] ≥70 IU/L), and evidence suggestive of hemolysis (total serum LDH ≥600 IU/L); class 2 requires similar criteria except

thrombocytopenia is moderate (>50,000 to ≤100,000/μL); and class 3 includes patients with mild thrombocytopenia (platelets >100,000 but

≤150,000/μL), mild hepatic dysfunction (AST and/or ALT ≥40 IU/L), and hemolysis (total serum LDH ≥600 IU/L)."[11]

[edit]Treatment

The only effective treatment is prompt delivery of the baby. Several medications have been investigated for the treatment of HELLP syndrome, but

evidence is conflicting as to whether magnesium sulfate decreases the risk of seizures and progress to eclampsia. The DIC is treated with fresh

frozen plasma to replenish the coagulation proteins, and the anemia may require blood transfusion. In mild

cases, corticosteroids andantihypertensives (labetalol, hydralazine, nifedipine) may be sufficient. Intravenous fluids are generally required. Hepatic

hemorrhage can be treated with embolization as well if life-threatening bleeding ensues.

The University of Mississippi standard protocol for HELLP includes corticosteroids.[12] However, a 2009 review found "no conclusive evidence"

supporting corticosteroid therapy,[1] and a 2010 systematic review by the Cochrane Collaboration also found "no clear evidence of any effect of

corticosteroids on substantive clinical outcomes" either for the mothers or for the newborns,[13]

[edit]Prognosis

The outcome for mothers with HELLP syndrome is generally good. With treatment, maternal mortality is about 1 percent. However complications

have been observed, including placental abruption, acute renal failure, subcapsular liver hematoma, and retinal detachment.[5]

[edit]Epidemiology

Its incidence is reported as 0.5-0.9% of all pregnancies, and 10-20% of women with severe preeclampsia.[1] HELLP usually occurs in Caucasian

women over the age of 25.[7]

[edit]History

HELLP syndrome was identified as a distinct clinical entity (as opposed to severe pre-eclampsia) by Dr. Louis Weinstein in 1982.[2] In a 2005

article, Weinstein wrote that the unexplained postpartum death of a woman who had hemolysis, abnormal liver function, thrombocytopenia, and

hypoglycemia motivated him to review the medical literature and to compile information on similar patients.[3] He noted that cases with features of

HELLP had been reported as early as 1954.[3][14]

HemolysisFrom Wikipedia, the free encyclopedia

This article is about medical aspects of hemolysis. For hemolysis in the culture of microorgranisms, see Hemolysis (microbiology).

"Laking" redirects here. For other uses, see Laking (disambiguation).

Hemolysis (or haemolysis)—from the Greek α ἷ μα  (aima, haema, hemo-) meaning "blood" and λύσις (lusis, lysis, -lysis) meaning a "loosing", "setting

free" or "releasing"[1]—is the rupturing of erythrocytes (red blood cells) and the release of their contents (hemoglobin) into surrounding fluid (e.g., blood

plasma). Hemolysis may occur in vivo or in vitro (inside or outside the body).

Contents

  [hide] 

1     In vivo (Inside the body)   

o 1.1      Streptococcus   

o 1.2      Enterococcus   

o 1.3      Staphylococcus   

o 1.4      Parasitic hemolysis   

o 1.5      Hemolytic disease of the newborn   

o 1.6      Hemolytic anemia   

o 1.7      Hemolytic crisis   

2     In vitro (lit. "in glass," but generally meaning outside the body)   

o 2.1      From specimen collection   

o 2.2      From mechanical blood processing during surgery   

o 2.3      From bacteria culture   

3     See also   

4     External links   

5     References   

[edit]In vivo (Inside the body)

In vivo hemolysis can be caused by a large number of medical conditions, including many Gram-positive bacteria (e.g., streptococcus, enterococcus,

and staphylococcus), some parasites (e.g., malaria), some autoimmune disorders (e.g., hemolytic disease of the newborn), and some genetic disorders

(e.g., sickle-cell disease or G6PD deficiency).

[edit]Streptococcus

Main article: Streptococcus

Many species of the genus Streptococcus cause hemolysis. Streptococcal bacteria species are classified according to their hemolytic properties.

Alpha-hemolytic species, including S. pneumoniae, S. mutans, and S. salivarius, reduce the iron in the hemoglobin (turning it dark green in culture).

Beta-hemolytic species, including S. pyogenes and S. agalactiae, completely rupture the red blood cells (visible as a halo in culture).

Gamma-hemolytic, or non-hemolytic, species do not cause hemolysis and rarely cause illness.

[edit]Enterococcus

Main article: enterococcus

The genus enterococcus includes lactic acid bacteria formerly classified as beta-hemolytic Group D in the genus streptococcus (see above), including E.

faecilis (S. faecalis), E. faecium (S. faecium), E. durans (S. durans), and E. avium (S. avium).

[edit]Staphylococcus

Main article: staphylococcus

Staphylococcus is another Gram-positive cocci. S. aureus, the most common cause of "staph" infections, is frequently beta-hemolytic.[2]

[edit]Parasitic hemolysis

Because the feeding process of the plasmodium parasites damages red blood cells, Malaria is sometimes called "parasitic hemolysis" in medical

literature.

[edit]Hemolytic disease of the newborn

Main article: hemolytic disease of the newborn

Hemolytic disease of the newborn is an autoimmune disease resulting from the mother's antibodies crossing the placenta to the fetus.

[edit]Hemolytic anemia

Main article: hemolytic anemia

Because in vivo hemolysis destroys the red blood cells, in uncontrolled chronic or severe cases it can lead to hemolytic anemia.

[edit]Hemolytic crisis

A hemolytic crisis, or hyperhemolytic crisis, is characterized by an accelerated rate of red blood cell destruction leading to anemia, jaundice,

and reticulocytosis.[3] Hemolytic crises are a major concern with sickle-cell disease and G6PD deficiency.

[edit]In vitro (lit. "in glass," but generally meaning outside the body)

Hemolysis of blood samples. Red blood cells without (left and middle) and with (right) hemolysis. If as little as 0.5% of the red blood cells are hemolyzed, the released

hemoglobin will cause the serum or plasma to appear pale red or cherry red in color.[4] Note that the hemolyzed sample is transparent, because there are no cells to scatter

light.

In vitro hemolysis can be caused by improper technique during collection of blood specimens, by the effects of mechanical processing of blood, or by

bacterial action in cultured blood specimens.

[edit]From specimen collection

Most causes of In vitro hemolysis are related to specimen collection. Difficult collections, unsecure line connections, contamination, and incorrect needle

size, as well as improper tube mixing and incorrectly filled tubes are all frequent causes of hemolysis. Excessive suction can cause the red blood cells to

be literally smashed on their way through the hypodermic needle owing to turbulence and physical forces. Such hemolysis is more likely to occur when a

patient's veins are difficult to find or when they collapse when blood is removed by a syringe or a modern vacuum tube. Experience and proper technique

are key for any phlebotomist or nurse to prevent hemolysis.

In vitro hemolysis during specimen collection can cause inaccurate laboratory test results by contaminating the surrounding plasma with the contents of

hemolyzed red blood cells. For example, the concentration of potassium inside red blood cells is much higher than in the plasma and so an elevated

potassium level is usually found in biochemistry tests of hemolyzed blood.

In vitro hemolysis can also occur in a blood sample because of prolonged storage or storage in incorrect conditions (i.e., too hot or too cold).

[edit]From mechanical blood processing during surgery

In some surgical procedures (especially some heart operations) where substantial blood loss is expected, machinery is used for intraoperative blood

salvage. A centrifuge process takes blood from the patient, washes the red blood cells with normal saline, and returns them to the patient's blood

circulation. Hemolysis may occur if the centrifuge rotates too quickly (generally greater than 500 rpm)—essentially this is hemolysis occurring outside of

the body. Unfortunately, increased hemolysis occurs with massive amounts of sudden blood loss, because the process of returning a patient's cells must

be done at a correspondingly higher speed to prevent hypotension, pH imbalance, and a number of other hemodynamic and blood level factors.

[edit]From bacteria culture

Main article: Hemolysis (microbiology)

Hemolysis from streptococcus. Examples of the blood culture patterns created by (from left) alpha-, beta- and gamma-hemolytic streptococci.

Visualizing the physical appearance of hemolysis in cultured blood samples may be used as a tool to determine the species of various Gram-positive

bacteria infections (e.g.,streptococcus).

Liver function testsFrom Wikipedia, the free encyclopedia

  (Redirected from Liver enzyme)

"LFTs" redirects here. For other uses, see LFT.

Liver function tests

Intervention

MeSH D008111

Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a

patient's liver.[1] The parameters measured include PT/INR, aPTT, albumin, billirubin (direct and indirect) and others. According to some, liver

transaminases (AST/ALT (SGOT/SGPT) are notliver function tests, but are biomarkers of liver injury in a patient with some degree of intact liver

function.[citation needed] Other sources include transaminases.[2][3] Mostliver diseases cause only mild symptoms initially, but it is vital that these

diseases be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed by a medical

technologist on a patient's serum or plasma sample obtained by phlebotomy. Some tests are associated with functionality (e.g., albumin); some

with cellular integrity (e.g., transaminase) and some with conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline

phosphatase). Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be

used to (1) detect the presence of liver disease, (2) distinguish among different types of liver disorders, (3) gauge the extent of known liver

damage, and (4) follow the response to treatment. Some or all of these measurements are also carried out (usually about twice a year for routine

cases) on those individuals taking certain medications- anticonvulsants are a notable example- in order to ensure that the medications are not

damaging the person's liver.

[edit]Standard liver panel

This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (November 2008)

[edit]Albumin (Alb)

Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total

protein; the remaining fraction is called globulin (including the immunoglobulins). Albumin levels are decreased in chronic liver

disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or

states of impaired protein catabolism, such as in Ménétrier's disease, may also lead to hypoalbuminaemia. The half-life of

albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function;

coagulation factors (see below) are much more sensitive

[edit]Alanine transaminase (ALT)

Alanine transaminase (ALT), also called Serum Glutamic Pyruvate Transaminase (SGPT) or Alanine aminotransferase (ALAT)

is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is

measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose.

Elevations are often measured in multiples of the upper limit of normal (ULN).

[edit]Aspartate transaminase (AST)

Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase

(ASAT) is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage,

but is also present in red blood cells, and cardiac and skeletal muscle and is therefore not specific to the liver. The ratio of AST

to ALT is sometimes useful in differentiating between causes of liver damage.[5][6] Elevated AST levels are not specific for liver

damage, and AST has also been used as a cardiac marker.

Reference range

3.5 to 5.3 g/dL

Reference range

9 to 52 IU/L[4]

Reference range

10 to 35 IU/L[4]

[edit]Alkaline phosphatase (ALP)

Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with

large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present

in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients

with Paget's disease.

[edit]Total bilirubin (TBIL)

Bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). The liver is responsible for clearing the

blood of bilirubin. It does this by the following mechanism: Bilirubin is taken up into hepatocytes, conjugated (modified to make

it water-soluble), and secreted into the bile, which is excreted into the intestine.

Increased total bilirubin causes jaundice, and can signal a number of problems:

1. Prehepatic: Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage.

2. Hepatic: Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g., reduced hepatocyte uptake, impaired

conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis.

3. Posthepatic: Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver

or in the bile duct).

[edit]Direct bilirubin (Conjugated Bilirubin)

The diagnosis is narrowed down further by looking at the levels of direct bilirubin.

If direct (i.e. conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin, and the location of the

problem is upstream of bilirubin excretion. Hemolysis, viral hepatitis, or cirrhosis can be suspected.

If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or

cancer should be suspected.

Reference range

30 to 120 IU/L[4]

Reference range

0.2–1.2 mg/dL

Reference range

0.1–0.4 mg/dL

[edit]Gamma glutamyl transpeptidase (GGT)

Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl

transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in

identifying the cause of an isolated elevation in ALP (GGT is raised in chronic alcohol toxicity).

[edit]Other tests commonly requested alongside LFTs

Pathophysiology sample values

BMP/ELECTROLYTES:

Na   +  =140 Cl   −  =100 BUN=20 /

Glu=150

K  +  =4 CO2=22 PCr=1.0 \

ARTERIAL BLOOD GAS:

HCO3-=24 paCO2=40 paO2=95 pH=7.40

ALVEOLAR GAS:

pACO2=36 pAO2=105 A-a g=10

OTHER:

Ca=9.5 Mg   2+   =2.0 PO4=1

CK=55 BE=−0.36 AG=16

SERUM OSMOLARITY/RENAL:

Reference range

0 to 42 IU/L[4]

PMO = 300 PCO=295 POG=5 BUN:Cr=20

URINALYSIS:

UNa   +  =80 UCl   −  =100 UAG=5 FENa=0.95

UK   +  =25 USG=1.01 UCr=60 UO=800

PROTEIN/GI/LIVER FUNCTION TESTS:

LDH=100 TP=7.6 AST=25 TBIL=0.7

ALP=71 Alb=4.0 ALT=40 BC=0.5

AST/ALT=0.6 BU=0.2

AF alb=3.0 SAAG=1.0 SOG=60

CSF:

CSF alb=30 CSF glu=60 CSF/S alb=7.5 CSF/S glu=0.4

[edit]5' Nucleotidase (5'NTD)

5' Nucleotidase is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a

substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.

[edit]Coagulation test (e.g., INR)

The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular

pathway of coagulation, comparing it to normal. Increased levels of INR means that blood is taking more time than usual to coagulate or clot. The

INR will be increased only if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired; it is not a

sensitive measure of liver function.

It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the

deficient factors) as they could bleed excessively.

[edit]Serum glucose (BG, Glu)

The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.

[edit]Lactate dehydrogenase (LDH)

Lactate dehydrogenase is an enzyme found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage.

[edit]See also

Reference ranges for blood tests

Elevated transaminases

Liver disorders  and liver diseases.

[edit]References

1. ̂  Lee, Mary (2009-03-10). Basic Skills in Interpreting Laboratory Data. ASHP. pp. 259–. ISBN 9781585281800. Retrieved 5 August 2011.

2. ̂  McClatchey, Kenneth D. (2002). Clinical laboratory medicine. Lippincott Williams & Wilkins. pp. 288–. ISBN 9780683307511. Retrieved 5 August 2011.

3. ̂  Mengel, Mark B.; Schwiebert, L. Peter (2005). Family medicine: ambulatory care & prevention. McGraw-Hill Professional.

pp. 268–. ISBN 9780071423229. Retrieved 5 August 2011.

4. ^ a b c d[broken citation]

5. ̂  Nyblom H, Berggren U, Balldin J, Olsson R (2004). "High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy

drinking". Alcohol Alcohol. 39(4): 336–339. doi:10.1093/alcalc/agh074. PMID 15208167.

6. ̂  Nyblom H, Björnsson E, Simrén M, Aldenborg F, Almer S, Olsson R (September 2006). "The AST/ALT ratio as an indicator of cirrhosis in patients with

PBC". Liver Int. 26 (7): 840–845. doi:10.1111/j.1478-3231.2006.01304.x. PMID 16911467.

[edit]External links

MeSH  Liver+function+tests

Overview  at Mayo Clinic

Abnormal Liver Function Tests

Overview of liver enzymes

ThrombocytopeniaFrom Wikipedia, the free encyclopedia

Thrombocytopenia

Classification and external resources

ICD-10 D   69.6   , P  61.0   

ICD-9 287.3, 287.4, 287.5

OMIM 188000 313900

DiseasesDB 27522

MedlinePlus 000586

MeSH D013921

Thrombocytopenia (or thrombopenia) is a relative decrease of platelets in blood.

A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood.[1] These limits are determined by the 2.5th lower and

upper percentile, so values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia is a platelet count below

50,000 per microliter.[2][3]

[edit]Signs and symptoms

Often, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine full blood count (or CBC, complete blood count).

Occasionally, there may be bruising, particularly purpura in the forearms, petechia (pinpoint hemorrhages on skin and mucous

membranes), nosebleeds and/or bleeding gums.

It is vital that a full medical history is elicited, to ensure the low platelet count is not due to a secondary process. It is also important to ensure that the

other blood cell types, such as red blood cells and white blood cells, are not also suppressed. Painless, round and pinpoint (1 to 3 mm in diameter),

petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue or yellow-green

bruises that vary in size and shape. They can occur anywhere on the body.

A person with thrombocytopenia may also complain of malaise, fatigue and general weakness (with or without accompanying blood loss). In acquired

thrombocytopenia, the patient's history may include the use of one or several offending drugs.

Inspection typically reveals evidence of bleeding (petechiae or ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Adults

may have large, blood-filled bullae in the mouth. If the person's platelet count is between 30,000 and 50,000/mm3, bruising with minor trauma may be

expected; if it is between 15,000 and 30,000/mm3, spontaneous bruising will be seen (mostly on the arms and legs).

[edit]Causes

Decreased platelet counts can be due to a number of disease processes:

[edit]Decreased production

Vitamin B 12 or folic acid deficiency

Leukemia  or myelodysplastic syndrome

Decreased production of thrombopoietin by the liver in liver failure.

Sepsis , systemic viral or bacterial infection

Dengue fever  can cause thrombocytopenia by direct infection of bone marrow megakaryocytes as well as immunological shortened platelet survival

Hereditary syndromes

Congenital amegakaryocytic thrombocytopenia  (CAMT)

Thrombocytopenia absent radius  syndrome

Fanconi anemia

Bernard-Soulier syndrome , associated with large platelets

May-Hegglin anomaly , the combination of thrombocytopenia, pale-blue leuckocyte inclusions, and giant platelets

Grey platelet syndrome

Alport syndrome

Wiskott–Aldrich syndrome

[edit]Increased destruction

Idiopathic thrombocytopenic purpura  (ITP)

Thrombotic thrombocytopenic purpura  (TTP)

Hemolytic-uremic syndrome  (HUS)

Disseminated intravascular coagulation  (DIC)

Paroxysmal nocturnal hemoglobinuria  (PNH)

Antiphospholipid syndrome

Systemic lupus erythematosus  (SLE)

Post-transfusion purpura

Neonatal alloimmune thrombocytopenia  (NAITP)

Splenic sequestration of platelets due to hypersplenism

Dengue fever  has been shown to cause shortened platelet survival and immunological platelet destruction

HIV-associated thrombocytopenia [4]

[edit]Medication-induced

platelets deficiency-inducing medications include:

Direct myelosuppression

Valproic acid

Methotrexate

Carboplatin

Interferon

Isotretinoin

Panobinostat

Other chemotherapy drugs

Singulair (montelukast sodium)

H2 blockers  and Proton-pump inhibitors have shown increased Thrombocytopenia symptoms, such as red dots near the bottom of the legs.[5]

Immunological platelet destruction

Drug binds Fab portion of an antibody. The classic example of this mechanism is the quinidine group of drugs. The Fc portion of the antibody

molecule is not involved in the binding process.

Drug binds to Fc, and drug-antibody complex binds and activates platelets. Heparin induced thrombocytopenia (HIT) is the classic example of

this phenomenon. In HIT, the heparin-antibody-platelet factor 4 (PF4) complex binds to Fc receptors on the surface of the platelet. Since Fc

portion of the antibody is bound to the platelets, they are not available to the Fc receptors of the reticulo-endothelial cells, so therefore this

system cannot destroy platelets as usual. This may explain why severe thrombocytopenia is not a common feature of HIT.

Abciximab  induced thrombocytopenia.

More extensive lists of thrombocytopenia-inducing medications are available.[6]

[edit]Other causes

Snakebites , particularly by pit vipers.[7]

Onyalai , a disease of unknown etiology seen only in parts of Africa, but suspected of being caused by poor nutrition or consumption of tainted food. [8]

[edit]Comparing coagulation tests

Condition Prothrombin time Partial thromboplastin time Bleeding time Platelet count

Vitamin K deficiency or warfarin prolonged normal or mildly prolonged unaffected unaffected

Disseminated intravascular coagulation prolonged prolonged prolonged decreased

von Willebrand disease unaffected prolonged prolonged unaffected

Hemophilia unaffected prolonged unaffected unaffected

Aspirin unaffected unaffected prolonged unaffected

Thrombocytopenia unaffected unaffected prolonged decreased

Liver failure, early prolonged unaffected unaffected unaffected

Liver failure, end-stage prolonged prolonged prolonged decreased

Uremia unaffected unaffected prolonged unaffected

Condition Prothrombin time Partial thromboplastin time Bleeding time Platelet count

Congenital afibrinogenemia prolonged prolonged prolonged unaffected

Factor V deficiency prolonged prolonged unaffected unaffected

Factor X deficiency as seen in amyloid purpura prolonged prolonged unaffected unaffected

Glanzmann's thrombasthenia unaffected unaffected prolonged unaffected

Bernard-Soulier syndrome unaffected unaffected prolonged decreased or unaffected

[edit]Diagnosis

Laboratory tests might include: full blood count, liver enzymes, renal function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and

peripheral blood smear.

If the cause for the low platelet count remains unclear, a bone marrow biopsy is usually recommended, to differentiate whether the low platelet count is

due to decreased production or peripheral destruction.

Thrombocytopenia in hospitalized alcoholics may be caused by splenomegaly, folate deficiency, and, most frequently, a direct toxic effect of alcohol on

production, survival time, and function of platelets. Platelet count begins to rise after 2 to 5 days' abstinence from alcohol. The condition is generally

benign, and clinically significant hemorrhage is rare.

Lab tests to determine the platelet count and clotting function may also be done. In severe thrombocytopenia, a bone marrow study can determine the

number, size and maturity of the megakaryocytes (the bone marrow cells that release mature platelets). This information may identify ineffective platelet

production as the cause of thrombocytopenia and rule out a malignant disease process at the same time.

[edit]Treatment

Treatment is guided by etiology and disease severity. The main concept in treating thrombocytopenia is to eliminate the underlying problem, whether that

means discontinuing suspected drugs that cause thrombocytopenia, or treating underlying sepsis. Diagnosis and treatment of serious thrombocytopenia is

usually directed by a hematologist.

Corticosteroids may be used to increase platelet production. Lithium carbonate or folate may also be used to stimulate the bone marrow production of

platelets. Platelet transfusions may be used to stop episodic abnormal bleeding caused by a low platelet count. However, if platelet destruction results

from an immune disorder, platelet infusions may have only a minimal effect and may be reserved for life-threatening bleeding.

Specific treatment plans often depend on the underlying etiology of the thrombocytopenia.

Condition Treatment

Thrombotic thrombocytopenic purpura

Treatment of thrombotic thrombocytopenic purpura is a medical emergency, since the hemolytic anemia and platelet activation can lead to renal failure and changes in the level of consciousness. Treatment of TTP was revolutionized in the 1980s with the application of plasmapheresis. According to the Furlan-Tsai hypothesis,[9][10] this treatment theoretically works by removing antibodies directed against the von Willebrand factor cleaving protease, ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease proteins to the patient, restoring a more physiological state of von Willebrand factor multimers. Patients with persistent antibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to explain the how plasmapheresis treats TTP.

Idiopathic thrombocytopenic purpura

Many cases of ITP can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts of under 50,000 are usually monitored with regular blood tests, and those with counts of under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with a platelet count this low. Any patient experiencing severe bleeding symptoms is also 

usually treated. The threshold for treating ITP has decreased since the 1990s, and hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000—though there are documented exceptions to this observation.

Treatments for ITP include:

Prednisone    and other corticosteroids

Intravenous immune globulin   

Splenectomy   

Danazol   

Eltrombopag   

Rituximab   

Romiplostim   

Thrombopoetin analogues have been tested extensively for the treatment of ITP. These agents had previously shown promise but had

been found to stimulate antibodies against endogenous thrombopoietin  or lead to thrombosis.

Romiplostim (trade name Nplate, formerly AMG 531) was found to be safe and effective for the treatment of ITP in refractory

patients, especially those who relapsed following splenectomy.[11][12][13]

Heparin-induced thrombocytopenia

Discontinuation of heparin is critical in a case of HITT. Beyond that, however, clinicians generally treat to avoid a thrombosis, and patients started directly on warfarin after a diagnosis of HITT are at excess risk of venous limb gangrene. For this reason, patients are usually treated with a type of blood thinner called a direct thrombin inhibitor such as lepirudin or argatroban, which are approved by the U.S. Food and Drug Administration (FDA). Other blood thinners sometimes used in this setting that are not FDA-approved for treatment of HITT include bivalirudin andfondaparinux. Platelet transfusions are not a routine component of the treatment of HITT, since thrombosis, not bleeding, is the usual associated problem in this illness.

Congenital amegakaryocytic thrombocytopenia

Bone Marrow/Stem Cell Transplant is the only thing that ultimately cures this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death until transplant is done, although this is not always the case.

[edit]Neonatal thrombocytopenia

Thrombocytopenia affects a few percent of newborns, and its prevalence in neonatal intensive care units (NICU) is high. Normally, its course is mild and it

resolves without consequences. Most of the cases of thrombocytopenia affect preterm birth infants and are results of placental insufficiency and/or fetal

hypoxia. The other causes are less frequent, e.g. alloimmune, genetic, autoimmune, infection, DIC.[14]

Thrombocytopenia that starts after the first 72 hours since birth is often the result of underlying sepsis or necrotising enterocolitis (NEC).[14] In the case of

infection the PCR tests may be useful for rapid pathogen identification and detection of antibiotic resistance genes. The possible pathogens may be

fungus, bacteria and viruses, for example: Cytomegalovirus (CMV),[14] Rubella virus,[14] HIV,[14] Staphylococcus sp.,[15] Enterococcus sp. ,[15] Streptococcus

agalactiae (GBS),[14] Streptococcus viridans,[16] Listeria monocytogenes,[17] Escherichia coli,[14][15] Haemophilus influenzae,[14] Klebsiella pneumoniae,

[15] Pseudomonas aeruginosa,[15][18] Yersinia enterocolitica,[18] Borrelia burgdorferi,[16] Candida sp.,[15] Toxoplasma gondii.[14] The severity of

thrombocytopenia might be correlated with the type of a pathogen; some research indicates that the most severe cases are related to fungal or gram-

negative bacterial infection.[15] The pathogen may be transmitted during birth[19] or prior to it, but also by breast feeding.[20][21][22] or during transfusion[23][24]

The interleukin-11 is being investigated as a potential drug for aiding thrombocytopenia management, especially in the cases of sepsis or necrotising

enterocolitis (NEC).[14]

[edit]Veterinary treatment

Thrombocytopenia caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections is treated with Lymphocyte T-Cell Immune

Modulator.

HELLP syndrome

HELLP syndrome is a group of symptoms that occur in pregnant women who have:

H -- hemolysis (the breakdown of red blood cells)

EL -- elevated liver enzymes

LP -- low platelet count

Causes

A cause for HELLP syndrome has not been found.

HELLP syndrome occurs in about 1 to 2 out of 1,000 pregnancies, and in 10-20% of pregnant women with severe preeclampsia or eclampsia.

Most often HELLP develops before the pregnancy is 37 weeks along. Sometimes it can develop in the week after the baby is born.

Many women have high blood pressure and are diagnosed with preeclampsia before they develop HELLP syndrome. However, in some cases,

HELLP symptoms are the first warning of preeclampsia and the condition is misdiagnosed as:

Flu or other viral illness

Gallbladder disease

Hepatitis

Idiopathic thrombocytopenic purpura  (ITP)

Lupus flare

Thrombotic thrombocytopenic purpura

Symptoms

Fatigue or feeling unwell

Fluid retention and excess weight gain

Headache

Nausea and vomiting that continues to get worse

Pain in the upper right part of the abdomen

Blurry vision

Nosebleed or other bleeding that won't stop easily (rare)

Seizures  or convulsions (rare)

Exams and Tests

During a physical examination, the doctor may discover:

Abdominal tenderness , especially in the right upper side

Enlarged liver

High blood pressure

Swelling in the legs

Liver function tests (liver enzymes) may be high. Platelet counts may be low. A CT scan may show bleeding into the liver.

Tests of the baby's health will be done.

Treatment

The main treatment is to deliver the baby as soon as possible, even if the baby is premature. Problems with the liver and other complications of

HELLP syndrome can quickly get worse and be harmful to both the mother and child.

Your doctor may induce labor by giving you drugs to start labor, or may perform a C-section.

You may also receive:

A blood transfusion if bleeding problems become severe

Corticosteroid medications to help the baby's lungs develop faster

Medications to treat high blood pressure

Outlook (Prognosis)

When the disease is not treated early, up to 1 out of 4 women develop serious complications. Without treatment, a small number of women die.

The death rate among babies born to mothers with HELLP syndrome depends on birth weight and the development of the baby's organs,

especially the lungs. (See also: Prematurity)

HELLP syndrome may return in up to 1 out of 4 future pregnancies.

Possible Complications

There can be complications before and after the baby is delivered, including:

Disseminated intravascular coagulation  (DIC) -- a clotting disorder that leads to excess bleeding (hemorrhage)

Fluid in the lungs (pulmonary edema)

Kidney failure

Liver hemorrhage and failure

Separation of the placenta from the uterine wall (placental abruption)

After the baby is born and HELLP syndrome has time to improve, most of these complications will go away.

When to Contact a Medical Professional

If symptoms of HELLP syndrome occur during pregnancy:

See your obstetrician immediately

Call the local emergency number (such as 911)

Get to the emergency room

Although there is no known way to prevent HELLP syndrome, it is important for all pregnant women to start prenatal care early and continue it

through the pregnancy. This allows the health care provider to find and treat conditions such as HELLP syndrome early.

HELLP Syndrome...A Pregnancy Complication

HELLP syndrome: A syndrome featuring a combination of "H" for hemolysis (breakage of red blood cells), "EL" for elevated liver enzymes,

and "LP" for low platelet count (an essential blood clotting element).

The HELLP syndrome is a recognized complication of preeclampsia and eclampsia (toxemia) of pregnancy, occuring in 25% of these

pregnancies.

Common symptoms in women with the HELLP syndrome include a general feeling of feeling unwell (malaise), nausea and/or vomiting, and

pain in the upper abdomen. Increased fluid in the tissues (edema) is also frequent. Protein is measurable in the urine of most women with

the HELLP syndrome. Blood pressure may be elevated. Occasionally, coma can result from seriously low blood sugar (hypoglycemia).

The first order of treatment of HELLP syndrome is management of the blood clotting issues. If fetal growth is restricted, urgent delivery can

be required. If the HELLP syndrome develops at or after 34 weeks of gestation or if the fetus' lungs are mature or mother's health is in

jeopardy, urgent delivery is the treatment.

After delivery, the mother's status is monitored closely. The HELLP syndrome can be complicated by liver rupture, anemia, bleeding, and

death. The HELLP syndrome can also develop during the early period after delivery of a baby.

Women with a history of HELLP syndrome are considered at increased risk for complications in future pregnancies.