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Thrombocytosis

Thrombocytosis refers to a hematological condition in which the accumulation of platelets causes many medical emergencies such as stroke and cardiac complications. Platelets are responsible for regulating and facilitating the mechanism of blood clot formation, also known as thrombus. The elevated level of platelets is associated with disorders of blood or bone marrow in which blood cells are produced. The abnormalities can lead to many hematological disorders, Thrombocytosis being one of the most noticed.


Classification and Clinical manifestations

Thrombocytosis can be classified in to two types depending upon the origin of its occurrence:

Primary thrombocytosis: Primary thrombocytosis is caused by abnormalities associated with bone marrow or blood. It is commonly known as essential thrombocythemia. This disorder is predominantly noticed in women and adults above the age of 55. The clinical symptoms associated with disease include erythromelalgia where there is redness of the arms and legs with burning sensation and pain. In addition to this, lightheadedness, nausea, weakness, lethargy, dizziness, frequent nosebleeds and bloody stools follow depending upon the stage of the thrombocytosis. Pathological smears usually indicate the presence of megakaryocytic cells in the blood smear, which are produced by the bone marrow in excess. Studies indicate the genetic evidence of the Janus kinase 2 (JAK 2)mutation in thrombocytic patients, which also associate, with neoplasms of proliferative origin leading to ischemia and heart attack.


Secondary Thrombocytosis: This form of thrombocytosis is reactive in nature and it is caused by the excessive production of the pro-inflammatory interleukins such as IL-1 and IL-6. In this condition, C reactive protein is noticed in excess in the serum and typically indicating the onset of inflammatory disease. It is one of the common conditions in the United States and the complications associated with it are related to vascular obstructions. Secondary thrombocytosis is caused because of various underlying conditions such as infections, trauma, splenectomy, malignancy and anemia associated with iron deficiency.


Diagnosis and Treatment

Thrombocytosis is diagnosed by blood tests to determine the amount of megakaryocytic in the blood film. Complete blood count with platelet amount evaluation along with C protein reactivity is studied. Splenomegaly is noticed in nearly 25% of patients. Abnormal platelet values may be over 2,000,000/mcL. The common medications prescribed for thrombocytosis are hydroxyurea, anagrelide and introns. Some of the noticed side effects are associated with leukemia and hence the dosage is very important to avoid additional complications such as dizziness, diarrhea and vomiting.


Paraneoplastic Syndrome

The first report of Paraneoplastic syndrome is attributed to a French physician, M Auche, who described the involvement in a peripheral nervous system in cancer patients in 1890. This syndrome is a group of signs and symptoms caused by a substance that is produced by a tumor, or in reaction to a tumor. Paraneoplastic syndrome is defined as a rare disorder triggered by a response to neoplasm of an immune system that is altered. These are clinical syndromes produced by tumor although they occur remotely from the tumor itself.


The symptoms may be of any nature – endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal or miscellaneous. Fever is the most common sign. Other clinical symptoms may be benign but syndromes could be varied; from a malignant carcinoid syndrome to Cushing syndrome. In cancer patients, the central nervous system involvement can be detected and it is a prominent manifestation of cancer.

Because of their protean manifestations, Paraneoplastic syndromes are managed by a medical team of physicians, including medical oncologists, surgeons, radiation oncologists, endocrinologists, hematologists, neurologists and dermatologists.


Causes

This syndrome can be due to a number of causes, including hormones or biologically active products, made by tumor, which blocks normal hormone, autoimmunity, immune-complex production and immune suppression. But, this is not caused by the primary tumor itself, or by its metastases, or by compression, infection, nutritional deficiency, or treatment of tumor.

Patients with family history of malignancies are at an increased risk and should be screened for cancer. Paraneoplastic syndromes occur typically among middle-aged to older patients. They are mostly diagnosed with cancers of the lung, breast, ovaries, or lymphatic system or lymphoma.

These symptoms sometimes appear before the diagnosis of a malignancy. When the tumor breaks immune tolerance and begins to attack the normal tissue expressing that protein, this syndrome become prominent.


Types of Paraneoplastic Syndrome

Due to the complexity of this syndrome, its clinical presentations may vary greatly. Hence, Paraneoplastic syndromes is divided into four main categories - endocrine, neurological, mucocutaneous, and hematological syndromes as well as a host of others including rheumatologic, renal, gastrointestinal, Cutaneous and miscellaneous.


Fever, dysgeusia, anorexia, and cachexia are included under miscellaneous category. Fever is associated with lymphomas, acute leukemias, sarcoma and carcinomas.

Rheumatologic syndrome includes polyarthritis, particularly in patients with myelomas, lymphomas, acute leukemia, malignant tumors of the colon, pancreas, prostrate. Scleroderma may precede the evidence of tumor. Widespread form of malignancies of breast, uterus and lung can be observed.

Renal syndrome is characterized by hypokalemic nephropathy, and it occurs in 50% of individuals with ACTH secreting tumors of the lung. Nephrotic syndrome is observed in patients with Hodgkin lymphoma, non Hodgkin lymphoma, malignancies of lung, thyroid, colon, breast, ovary and pancreatic head.

Watery diarrhea and electrolyte imbalance, leads to asthenia, confusion and exhaustion, all characteristic of gastrointestinal syndromes. Severe prostaglandins lead to malabsorption and unavailability of nutrients.


Hematologic syndromes are related to anemia, thrombocytosis, disseminated intravascular coagulation, and leukemoid reactions from several types of cancers. Leukemoid reactions due to immature white blood cells in the blood stream are accompanied by hypereosinophilia and itching.

Cutaneous syndromes are manifested by itching and flushes, alopecia, or hypertrichosis. Blackish pigmentation of the skin usually occurs in patients with metastatic melanomas or pancreatic tumors.

Endocrine syndromes resemble common endocrine disorders. Increased serum and urine cortisol concentrations are common examples of this malignancy.


Neurologic or neuromuscular syndromes relate to cancers and such disorders affect 6% of all patients with cancer. Neuromuscular symptoms mimic common neurological conditions. Myasthenia gravis is a common Paraneoplastic syndrome in patients with thymoma, a malignancy arising from epithelial cells of the thymus.

Paraneoplastic limbic encephalitis is characterized by depression, seizures, irritability and short term memory loss and neurologic symptoms rapidly resemble dementia.

Paraneoplastic cerebellar degeneration causes gait difficulties, dizziness, nausea and diplopia. Sensory neuropathy affects lower and upper extremities and there is progressive memory loss, either symmetric or asymmetric.


Diagnosis

As Paraneoplastic syndromes may evolve over weeks to months, they usually stabilize regardless whether the patient's underlying condition improves or worsens. Since this is the first manifestation of cancer, patients should undergo investigation for cancer. Other diagnoses are membrane disease, dementia, encephalopathy, encephalitis, myelitis, anemia, bone marrow failure, chronic fatigue syndrome, mixed connective tissue disease, polycythemia vera and polymyalgia rheumatica among others.

Complete laboratory tests in blood, urine, cerebrospinal fluid, protein electrophoresis, assays for auto antibodies, Endoscopy and imaging studies including whole body scans and FDG-PET scans are prescribed to detect extremely small tumors especially useful for patients with neurologic diseases.


Treatment of Paraneoplastic Syndrome

Treatment for this syndrome varies depending upon the type and location of tumors. The first option of treatment of the underlying tumor is by therapeutic protocols, a combination of surgery, radiation, chemotherapy. Second therapeutic option is for patients with clearly identifiable antibodies by intravenous immunoglobulins, steroids, or plasma exchange.

Surgical treatment is typically directed toward the underlying neoplasm although some Paraneoplastic disorders may resolve rapidly without surgery on the primary tumor.



Bone Marrow Aspiration

Bone marrow refers to the spongy tissue that is found inside the larger bones such as spine, breast bone, hips, ribs, legs and skull. Marrow has two parts – both solid and liquid. If the solid portion of the bone is sampled, it is called biopsy. Aspiration procedure is used to collect the liquid part of the marrow.


Both the procedures show whether the bone marrow is healthy and making normal amounts of blood cells. This procedure is normally used by doctors to diagnose and monitor blood and marrow diseases, including cancer. In bone marrow aspiration, the doctor uses a needle to draw a sample of the fluid portion. For a biopsy, a larger needle is used to take the sample of the solid part.

Most often bone marrow aspiration and bone biopsy is done at once. Together, they make the bone marrow examination. Although they are different procedures, they offer complementary information about bone marrow cells.


Why is it done?

Bone marrow aspiration and biopsy offer detailed information about the condition of the bone marrow and blood cells. In case the blood tests indicate that cell counts are abnormal, and information is not sufficient about a suspected problem, this is done. The doctor may perform bone marrow exam to diagnose a disease condition involving the bone marrow or blood cells:


  • To determine a disease progression
  • To check the iron levels and metabolism and
  • To monitor treatment of a disease.

Pre bone marrow aspiration procedure

It is imperative to inform the doctor about any medications and supplements the patient is consuming. This can increase the risk of bleeding after a bone marrow aspiration. In case of anxiety or worry, better talk to the health care provider so that a sedative medication could be given before the aspiration in addition to a numbing agent through local anesthesia at the site where the needle is inserted.

Bone marrow aspiration is done in a hospital, a clinic or in a doctor's room. A specialist in blood disorders – a hematologist – or an oncologist, who is a specialist in cancer does the procedure with a nurse and a trained technologist. It usually takes about half an hour for the exam and if any intravenous sedation is given, extra time is taken for pre and post procedure care.

The patient's blood pressure and heart rate are checked. Some form of anesthesia is administered before the bone marrow aspiration as it can be painful. For many, local anesthesia is sufficient. You will be fully awake during the aspiration, but the site is numbed to reduce pain. If you are quite anxious, intravenous IV sedation is given before the marrow procedure.


Bone marrow aspiration procedure

The area for inserting the biopsy needle is marked and cleaned. The bone marrow fluid (aspirate) is usually collected from the top ridge of the back of the hipbone, and if it is done from the breast bone or the front of the hip near the groin. In young children and kids, the sample is taken from the lower leg bone, just below the knee. The patient will be made to lie down on the abdomen or side.

The bone marrow aspiration is usually done before the biopsy. A small incision is made to insert the needle easier. A hollow needle is inserted through the bone and into the bone marrow. Several samples are taken and aspiration takes only a few minutes. While the health care team ensures that sufficient quantity of sample is drawn, sometimes a 'dry tap' may occur, that is fluid cannot be withdrawn. The needle is moved for another attempt.


Post aspiration procedure

After the bone marrow exam, pressure is applied to the where the needle was inserted to stop the bleeding. A smaller bandage is placed on the site. If local anesthesia had been administered the patient is asked to lie back for 10-15 minutes and apply pressure on the biopsy site. In case, IV sedation had been given, you are taken into a recovery area as sedatives may cause impaired judgment, memory lapses or slowed response.

Tenderness may be felt for a week or more after the bone marrow exam, and the doctor administers pain reliever. You need to keep the bandage dry for 24 hours and not shower or bathe, or swim or use the hot tub. It is okay to get the aspiration site wet after 24 hours. In case bleeding soaks through the bandage, or does not stop even with direct pressure, consult the doctor. The doctor also needs to be contacted if there is persistent fever, worsening pain, swelling at the procedure site and increasing redness or drainage at the procedure site. Also it is advised to avoid rigorous activity for a couple of days to minimize bleeding and discomfort.


Results from bone marrow aspiration

The sample is sent to a laboratory for analysis. The results are available in a few days. The pathologist or hematologist evaluates the samples to check the health of the marrow and if it has enough healthy blood cells and also for abnormal cells. The doctor confirms or rules out a diagnosis and how advanced the disease is or if the treatment is working. Sometimes, follow-up tests are done.


Risks of bone marrow examination

This is a safe procedure and complications are rare. But some complications include:

Excessive bleeding which can happen in people with low platelet count.
Infection in those with weakened immune systems.
Discomfort that could be long lasting in the biopsy site.
Heart and lung problems can be caused due to penetration of the breastbone.
Sedation can cause allergic reaction, nausea and irregular heartbeats in some.


Uses of bone marrow exams

These are used for many conditions including:


  • Anemia
  • Bone marrow disorders which include myelodysplastic syndrome and myelofibrosis.
  • Blood cell conditions such as Leukopenia, leukocytosis, thrombocytopenia, thrombocytosis, pancytopenia and polycythemia – which produce too few or too many of certain types of blood.
  • Cancers of the bone marrow or of blood including leukemia, lymphomas and multiple myeloma.
  • Cancers that have spread to other areas including breast.
  • Hemochromatosis and
  • Infections.

While problems with bone marrow can create lasting and serious health problems, bone marrow exams, such as aspiration and biopsy are important to help determine the status and extent of problems in the cells to evaluate and determine further treatment and management.


Tags: #Thrombocytosis #Paraneoplastic Syndrome #Bone Marrow Aspiration
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Collection of Pages - Last revised Date: October 14, 2024