Thrombocytopenia is a condition characterized by abnormally low levels of
platelets, also known as thrombocytes, in the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
. It is the most common
coagulation disorder among
intensive care patients and is seen in a fifth of medical patients and a third of surgical patients.
A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (μl) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/μl. Thrombocytopenia can be contrasted with the conditions associated with an abnormally ''high'' level of platelets in the blood -
thrombocythemia (when the cause is unknown), and
thrombocytosis (when the cause is known).
Signs and symptoms
Thrombocytopenia usually
has no symptoms and is picked up on a routine
complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and ...
. Some individuals with thrombocytopenia may experience external bleeding, such as
nosebleeds or bleeding
gums
The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health.
Structure
The gums are part of the soft tissue li ...
. Some women may have heavier or longer
periods or breakthrough bleeding.
Bruising
A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close ...
, particularly
purpura
Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...
in the forearms and
petechiae in the feet, legs, and
mucous membranes, may be caused by spontaneous bleeding under the skin.
Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. Ensuring that the other blood cell types, such as
red blood cells and
white blood cells, are not also suppressed, is also important.
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 areas of skin that vary in size and shape. They can occur anywhere on the body.
A person with this disease may also complain of
malaise,
fatigue, and general weakness (with or without accompanying blood loss). Acquired thrombocytopenia may be associated with the use of certain 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/μl, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/μl, spontaneous bruising will be seen (mostly on the arms and legs).
Causes
Thrombocytopenia can be inherited or acquired.
Decreased production
Abnormally low platelet production may be caused by:
*
Dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
,
vitamin B12 or
folic acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing a ...
deficiency
*
Leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
,
myelodysplastic syndrome, or
aplastic anemia
Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red bloo ...
* Decreased production of
thrombopoietin by the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
in
liver failure
*
Sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, systemic
viral or
bacterial infection
*
Leptospirosis
* Hereditary syndromes
[Almazni I, Stapley R, Morgan NV (2019) Inherited Thrombocytopenia: Update on genes and genetic variants which may be associated With bleeding. Front Cardiovasc Med]
**
ACTN1-related thrombocytopenia
**
Amegakaryocytic thrombocytopenia with radio-ulnar synostosis
**
ANKRD26 related thrombocytopenia
**
Autosomal dominant thrombocytopenia
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...
**
Bernard–Soulier syndrome
Bernard–Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder that is caused by a deficiency of the '' glycoprotein Ib-IX-V complex'' (GPIb-IX-V), the receptor for von Willebrand factor. The incidence of BSS is estimated to be ...
(associated with
giant platelet disorder)
**
Congenital amegakaryocytic thrombocytopenia
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited disorder.
Presentation
The primary manifestations are thrombocytopenia and megakaryocytopenia, or low numbers of platelets and megakaryocytes. There is an absence of megakaryo ...
**
Congenital amegakaryocytic thrombocytopenia and radioulnar synostosis
**
CYCS-related thrombocytopenia
**
Epstein syndrome
Epstein syndrome is a rare genetic disease characterized by a mutation in the MYH9 gene in nonmuscle myosin. This disease affects the patient's renal system and can result in kidney failure. Epstein Syndrome was first discovered in 1972 when two ...
(associated with giant platelet disorder)
**
ETV6 related thrombocytopenia
ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ''ETV6'' (previously known as ''TEL'') gene. The ETV6 protein regulates the development and growth of diverse cell types, particularl ...
**
Fanconi anemia
Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of no ...
**
Filaminopathies A
**
FYB related thrombocytopenia
FYN binding protein (FYB-120/130), also known as FYB, ADAP (Adhesion and degranulation-promoting adapter protein), and SLAP-130 ( SLP-76-associated phosphoprotein) is a protein that is encoded by the ''FYB'' gene in humans. The protein is express ...
**
Glanzmann's thrombasthenia
**
GNE myopathy with congenital thrombocytopenia GNE may refer to:
* Equatorial Guinea, ITU country code
* GNE (encyclopedia), a free content encyclopedia
* GNE (gene)
* Ganang language, spoken in Nigeria
* Genesis Energy Limited, a New Zealand energy company
* Go North East
Go North East o ...
**
Gray platelet syndrome (associated with giant platelet disorder)
**
Harris platelet syndrome (associated with giant platelet disorder)
**
Macrothrombocytopenia and hearing loss
**
May–Hegglin anomaly
May–Hegglin anomaly (MHA), is a rare genetic disorder of the blood platelets that causes them to be abnormally large.
Presentation
In the leukocytes, the presence of very small rods (around 3 micrometers), or Döhle-like bodies can be seen in ...
(associated with giant platelet disorder)
**
MYH9
Myosin-9 also known as myosin, heavy chain 9, non-muscle or non-muscle myosin heavy chain IIa (NMMHC-IIA) is a protein which in humans is encoded by the ''MYH9'' gene.
Non-muscle myosin IIA (NM IIA) is expressed in most cells and tissues where i ...
-related disease (associated with giant platelet disorder)
**
PRKACG-related thrombocytopenia
**
Paris-Trousseau thrombocytopenia
Paris-Trousseau syndrome (PTS) is an inherited disorder characterized by mild hemorrhagic tendency associated with 11q chromosome deletion. It manifests as a granular defect within an individual's platelets. It is characterized by thrombocytes wi ...
/
Jacobsen syndrome
**
Sebastian syndrome
Sebastian may refer to:
People
* Sebastian (name), including a list of persons with the name
Arts, entertainment, and media
Films and television
* ''Sebastian'' (1968 film), British spy film
* ''Sebastian'' (1995 film), Swedish drama film
...
**
SLFN14-related thrombocytopenia
**
Stormorken syndrome
**
TRPM7-related thrombocytopenia
**
Thrombocytopenia absent radius
TAR syndrome (thrombocytopenia with absent radius) is a rare genetic disorder that is characterized by the absence of the radius bone in the forearm and a dramatically reduced platelet count.
Signs and symptoms
* Presents with symptoms of thr ...
syndrome
**
Tropomyosin 4-related thrombocytopenia
Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons.
Tropomyosin and the actin skeleton
All organisms contain organelles that provide physical integrity to their cells. These type of organelles ar ...
**
TUBB1-related thrombocytopenia
**
Upshaw–Schulman syndrome
**
Wiskott–Aldrich syndrome
Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the ecz ...
**
X-linked thrombocytopenia
**
X-linked thrombocytopenia with thalassemia
Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...
Increased destruction
Abnormally high rates of platelet destruction may be due to immune or nonimmune conditions, including:
*
Immune thrombocytopenic purpura
*
Thrombotic thrombocytopenic purpura
*
Hemolytic–uremic syndrome
Hemolytic–uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems ...
*
Disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...
*
Paroxysmal nocturnal hemoglobinuria
*
Antiphospholipid syndrome
*
Systemic lupus erythematosus
*
Post-transfusion purpura Post-transfusion purpura (PTP) is a delayed adverse reaction to a blood transfusion or platelet transfusion that occurs when the body has produced alloantibodies to the allogeneic transfused platelets' antigens. These alloantibodies destroy the pa ...
*
Neonatal alloimmune thrombocytopenia
*
Hypersplenism
*
Dengue fever
*
Gaucher's disease
*
Zika virus
Medication-induced
These medications can induce thrombocytopenia through direct myelosuppression:
*
Valproic acid
*
Methotrexate
*
Carboplatin
Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used ...
*
Interferon
*
Isotretinoin
Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication primarily used to treat severe acne. It is also used to prevent certain skin cancers (squamous-cell carcinoma), and in th ...
*
Panobinostat
*
H2 blockers and
proton-pump inhibitors
Other causes
* Laboratory error, possibly due to the anticoagulant
EDTA in CBC specimen tubes; a ''citrated'' platelet count is a useful follow-up study
*
Snakebite
*
Niacin
Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...
toxicity
*
Lyme disease
Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the '' Borrelia'' bacterium, which is spread by ticks in the genus '' Ixodes''. The most common sign of infection is an expanding red rash, known as erythema ...
*
Thrombocytapheresis (also called plateletpheresis)
*
Niemann–Pick disease
Niemann–Pick disease is a group of severe inherited metabolic disorders, in which sphingomyelin accumulates in lysosomes in cells (the lysosomes normally degrade material that comes from out of cells).
These disorders involve the dysfunctional ...
Diagnosis
Laboratory tests for thrombocytopenia might include
full blood count,
liver enzymes,
kidney function, vitamin B
12 levels, folic acid levels,
erythrocyte sedimentation rate
The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
, and peripheral blood smear. If the cause for the low platelet count remains unclear, a
bone marrow biopsy is usually recommended to differentiate cases of decreased platelet production from cases of peripheral platelet destruction.
Thrombocytopenia in hospitalized alcoholics may be caused by
spleen enlargement,
folate deficiency
Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folat ...
, and most frequently, the 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.
In severe thrombocytopenia, a bone marrow study can determine the number, size, and maturity of the
megakaryocytes. This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time.
Treatment
Treatment is guided by the severity and specific cause of the disease. Treatment focuses on eliminating the underlying problem, whether that means discontinuing drugs suspected to cause it 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 platelet production in the bone marrow.
Platelet transfusions
Platelet transfusion
Platelet transfusion, also known as platelet concentrate, is used to prevent or treat bleeding in people with either a low platelet count or poor platelet function. Often this occurs in people receiving cancer chemotherapy. Preventive transfus ...
s may be suggested for people who have a low platelet count due to thrombocytopenia.
Thrombotic thrombocytopenic purpura
Treatment of
thrombotic thrombocytopenic purpura (TTP) is a medical emergency, since the associated
hemolytic anemia and platelet activation can lead to kidney 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, this treatment works by removing
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
against the
von Willebrand factor-cleaving
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
to the patient, restoring a normal level 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 how plasmapheresis treats TTP.
Immune thrombocytopenic purpura
Many cases of
immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura, can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts under 50,000/μl are usually monitored with regular blood tests, and those with counts under 10,000/μl are usually treated, as the risk of serious spontaneous bleeding is high with such low platelet counts. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s;
hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000/μl, although exceptions to this observation have been documented.
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
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, ...
thrombopoietin or lead to
thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...
.
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.
Heparin-induced thrombocytopenia
Discontinuation of heparin is critical in a case of heparin-induced thrombocytopenia (HIT). Beyond that, however, clinicians generally treat to avoid thrombosis. Treatment may include a
direct thrombin inhibitor, such as
lepirudin or
argatroban. Other "
blood thinners
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
" sometimes used in this setting include
bivalirudin and
fondaparinux
Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.
...
.
Platelet transfusion
Platelet transfusion, also known as platelet concentrate, is used to prevent or treat bleeding in people with either a low platelet count or poor platelet function. Often this occurs in people receiving cancer chemotherapy. Preventive transfus ...
s are not routinely used to treat HIT because thrombosis, not bleeding, is the primary problem.
Warfarin is not recommended until platelets have normalized.
[
]
Congenital amegakaryocytic thrombocytopenia
Bone marrow/stem cell transplants are the only known cures for this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death before the transplant can be performed, although this is not always the case.
Human-induced pluripotent stem cell-derived platelets
Human-induced pluripotent stem cell-derived platelets is a technology currently being researched by the private sector, in association with the Biomedical Advanced Research and Development Authority
The Biomedical Advanced Research and Development Authority (BARDA) is a U.S. Department of Health and Human Services (HHS) office responsible for the procurement and development of medical countermeasures, principally against bioterrorism, inc ...
and the U.S. Department of Health and Human Services
The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the U.S. federal government created to protect the health of all Americans and providing essential human services. Its motto is " ...
, that would create platelets outside the human body.
Neonatal thrombocytopenia
Thrombocytopenia affects a few newborns, and its prevalence in neonatal intensive care units is high. Normally, it is mild and resolves without consequences. Most cases affect preterm birth infants and result from placental insufficiency and/or fetal hypoxia. Other causes, such as alloimmunity, genetics, autoimmunity, and infection, are less frequent.
Thrombocytopenia that starts after the first 72 hours, since birth is often the result of underlying sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
or necrotizing enterocolitis
Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects premature or very low birth weight infants.Gephart S.M., Quinn M. A call to action to fight for equity and end necrotizing enterocolitis disparities. ''Adv. Neonata ...
. In the case of infection, polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
tests may be useful for rapid pathogen identification and detection of antibiotic-resistance genes. Possible pathogens include viruses (e.g. cytomegalovirus, rubella virus, HIV), bacteria (e.g. '' Staphylococcus'' spp., '' Enterococcus'' spp., '' Streptococcus agalactiae'', '' Listeria monocytogenes'', ''Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'', ''Haemophilus influenzae
''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bact ...
'', '' Klebsiella pneumoniae'', ''Pseudomonas aeruginosa
''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...
'', ''Yersinia enterocolitica
''Yersinia enterocolitica'' is a Gram-negative, bacillus-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29° C (72–84 °F), but becomes nonmotile at normal human body temperature. ''Y. enterocolit ...
''), fungi (e.g. '' Candida'' spp.), and '' Toxoplasma gondii''. The severity of thrombocytopenia may be correlated with pathogen type; some research indicates that the most severe cases are related to fungal or Gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
bacterial infection. The pathogen may be transmitted during or before birth, by breast feeding, or during transfusion. Interleukin-11
Interleukin 11 (IL-11) is a protein that in humans is encoded by the ''IL11'' gene.
IL-11 is a cytokine and first isolated in 1990 from bone marrow-derived fibrocyte-like stromal cells. It was initially thought to be important for hematopoiesi ...
is being investigated as a drug for managing thrombocytopenia, especially in cases of sepsis or necrotizing enterocolitis.
References
External links
{{Medicine
Coagulopathies
Medical signs
Hematopathology