“In 1986, President Reagan recognized March as “National Hemophilia Month” which has since been changed to #BleedingDisordersAwarenessMonth to be inclusive of all #bleedingdisorders. We’ll be posting facts throughout the month to honor our history and raise awareness about all #bleedingdisorders. Hemophilia is usually an inherited bleeding disorder in which the blood does not clot properly. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery.”

World Federation of Hemophilia – WFH (https://www.hemophiliafed.org/resource/bleeding-disorders-awareness-month/)

What is this condition?

Hemophilia is a bleeding disorder characterized by low levels of clotting factor proteins. Correct diagnosis of Hemophilia is essential to providing effective treatment. Blood Center of Wisconsin offers one of the largest diagnostic menus to accurately and confidently diagnose Hemophilia.

The X and Y chromosomes are called sex chromosomes. The gene for hemophilia is carried on the X chromosome. Hemophilia is inherited in an X-linked recessive manner.  Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). That means if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. It also means that fathers cannot pass hemophilia on to their sons.

But because daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, most likely they will inherit a healthy X chromosome from their father and not have hemophilia. A daughter who inherits an X chromosome that contains the gene for hemophilia is called a carrier. She can pass the gene on to her children. Hemophilia can occur in daughters, but is rare.

For a female carrier, there are four possible outcomes for each pregnancy:

1. A girl who is not a carrier
2. A girl who is a carrier
3. A boy without hemophilia
4. A boy with hemophilia

Hemophilia is an X-linked inherited bleeding disorder caused by mutation of the F8 gene that encodes for coagulation factor VIII or the F9 gene that encodes for coagulation factor IX. The degree of plasma factor deficiency correlates with both the clinical severity of disease and genetic findings. Severe hemophilia is characterized by plasma factor VIII or factor IX levels of under 1 IU/dl. Moderate and mild hemophilia are characterized by factor VIII or factor IX levels of 1-5 IU/dL or 6 – 40 IU/dL, respectively. Genetic analysis is useful for identification of the underlying genetic defect in males with severe, moderate or mild hemophilia and for determination of carrier status in the female individuals within their families. Additionally, data is emerging regarding the correlation between a patients mutation status and the risk of that patient developing an inhibitor.

People with hemophilia A often, bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts, dental procedures or trauma. How frequently a person bleeds and the severity of those bleeds depends on how much FVIII is in the plasma, the straw-colored fluid portion of blood.

Normal plasma levels of FVIII range from 50% to 150%. Levels below 50%, or half of what is needed to form a clot, determine a person’s symptoms.

• Mild hemophilia A-  6% up to 49% of FVIII in the blood. People with mild hemophilia Agenerally experience bleeding only after serious injury, trauma or surgery. In many cases, mild hemophilia is not diagnosed until an injury, surgery or tooth extraction results in prolonged bleeding. The first episode may not occur until adulthood. Women with mild hemophilia often experience menorrhagia, heavy menstrual periods, and can hemorrhage after childbirth.
• Moderate hemophilia A. 1% up to 5% of FVIII in the blood. People with moderate hemophilia A  tend to have bleeding episodes after injuries. Bleeds that occur without obvious cause are called spontaneous bleeding episodes.
• Severe hemophilia A.  <1% of FVIII in the blood. People with severe hemophilia A experience bleeding following an injury and may have frequent spontaneous bleeding episodes, often into their joints and musclesHemophilia A and B are diagnosed by measuring factor clotting activity. Individuals who have hemophilia A have low factor VIII clotting activity. Individuals who have hemophilia B have low factor IX clotting activity.Genetic testing is usually used to identify women who are carriers of a FVIII or FIX gene mutation, and to diagnose hemophilia in a fetus during a pregnancy (prenatal diagnosis). It is sometimes used to diagnose individuals who have mild symptoms of hemophilia A or B.There is currently no cure for hemophilia. Treatment depends on the severity of hemophilia.People who have moderate to severe hemophilia A or B may need to have an infusion of clotting factor taken from donated human blood or from genetically engineered products called recombinant clotting factors to stop the bleeding. If the potential for bleeding is serious, a doctor may give infusions of clotting factor to avoid bleeding (preventive infusions) before the bleeding begins. Repeated infusions may be necessary if the internal bleeding is serious. When a person who has hemophilia has a small cut or scrape, using pressure and a bandage will take care of the wound. An ice pack can be used when there are small areas of bleeding under the skin.
• When bleeding has damaged joints, physical therapy is used to help them function better. Physical therapy helps to keep the joints moving and prevents the joints from becoming frozen or badly deformed. Sometimes the bleeding into joints damages them or destroys them. In this situation, the individual may be given an artificial joint.
• Treatment may involve slow injection of a medicine called desmopressin (DDAVP) by the doctor into one of the veins. DDAVP helps to release more clotting factor to stop the bleeding. Sometimes, DDAVP is given as a medication that can be breathed in through the nose (nasal spray).
• Diagnosing this condition:
• Hemophilia is diagnosed with blood tests to determine if clotting factors are missing or at low levels, and which ones are causing the problem. If you have a family history of hemophilia, it is important that your doctors know the clotting factor your relatives are missing.
• Treatment of the condition:
• Genetic testing is also available for the factor VIII gene and the factor IX gene. Genetic testing of the FVIII gene finds a disease-causing mutation in up to 98 percent of individuals who have hemophilia A. Genetic testing of the FIX gene finds disease-causing mutations in more than 99 percent of individuals who have hemophilia B.
• Researchers have been working to develop a gene replacement treatment (gene therapy) for Hemophilia A. Research of gene therapy for hemophilia A is now taking place. The results are encouraging. Researchers continue to evaluate the long-term safety of gene therapies. The hope is that there will be a genetic cure for hemophilia in the future.

How Sarcoidosis can be diagnosed:

• biopsy of the lungs, liver, skin, or other affected organs to check for granulomas
• Blood tests, including complete blood counts, to check hormone levels and to test for other conditions that may cause sarcoidosis
• Bronchoscopy, which may include rinsing an area of the lung to get cells or using a needle to take cells from the lymph nodes in the chest
• Chest X-ray to look for granulomas in the lungs and heart and determine the stage of the disease. Often, sarcoidosis is found because a chest X-ray is performed for another reason.
• Neurological tests, such as electromyography, evoked potentials, spinal taps, or nerve conduction tests, to detect problems with the nervous system caused by sarcoidosis
• Eye exam to look for eye damage, which can occur without symptoms in a person with sarcoidosis
• Gallium scan external link , which uses a radioactive material called gallium to look for inflammation, usually in the eyes or lymph nodes.
• High-resolution computed tomography (CT) scan to look for granulomas
• Magnetic resonance imaging (MRI) to help find granulomas. Learn more in our Chest MRI Health Topic.
• Positron electron tomography (PET) scan, a type of imaging that can help find granulomas
• Pulmonary function tests to check whether you have breathing problems
• Ultrasound to look for granulomas

There is a staging to Sarcoidosis:

“Sarcoidosis is considered a rare disease. There are usually fewer than 200,000 cases of sarcoidosis at any given time in the U.S.

Research suggests that a combination of genetics and environmental factors cause sarcoidosis, but its exact cause is unknown. We think certain people are more likely to have their immune system overreact to certain triggers (antigens), like bacteria and viruses. Despite the immune system’s involvement, sarcoidosis isn’t considered an autoimmune disorder.

Since we don’t know for sure which combination of genes and triggers causes sarcoidosis, it’s impossible to predict who will get it.”

Cleveland Clinic (https://my.clevelandclinic.org/health/diseases/11863-sarcoidosis#:~:text=Sarcoidosis%20is%20a%20condition%20that%20causes%20your%20immune%20system%20to,fibrosis%2C%20causing%20permanent%20lung%20scarring.)

Lung lesions – 95% Thoracic lymph nodes – 50% Skin lesions – 30%  Eyes – 30%

Inflammatory Disease- Sarcoidosis or Sarcoid is a inflammatory disease that consists of granuloma.

Wide Spread Disease- Disease is wide spread in multiple organs.

• The Sarcoidosis disease tends to come and go all of a sudden.
• Disease may progressively develop as a serious illness.
• Patient may experience several relapse throughout the life.

• Sarcoidosis or Sarcoid is a gradual progressive disease.
• Microscopic lumps called granulomas start to appear in the affected organs.¹
• In most of the cases, these granulomas tend to clear with or without treatments.
• There are few instances where granuloma grows in size and continues to be a part of the organ.
• Granuloma eventually ends up as fibrotic lump but may cause several complications.

Causes

Doctors don’t know the exact cause of sarcoidosis. Some people appear to have a genetic predisposition to develop the disease, which may be triggered by bacteria, viruses, dust or chemicals.

This triggers an overreaction of your immune system and immune cells begin to collect in a pattern of inflammation called granulomas. As granulomas build up in an organ, the function of that organ can be affected.

Risk factors

While anyone can develop sarcoidosis, factors that may increase your risk include:

• Age and sex. Sarcoidosis often occurs between the ages of 20 and 40. Women are slightly more likely to develop the disease.
• Race. African-Americans have a higher incidence of sarcoidosis than do white Americans. Also, sarcoidosis may be more severe and may be more likely to recur and cause lung problems in African-Americans.
• Family history. If someone in your family has had sarcoidosis, you’re more likely to develop the disease.

Complications

For most people, sarcoidosis resolves on its own with no lasting consequences. But sometimes it causes long-term problems.

• Lungs. Untreated pulmonary sarcoidosis can lead to permanent scarring in your lungs, making it difficult to breathe.
• Eyes. Inflammation can affect almost any part of your eye and can eventually cause blindness. Rarely, sarcoidosis also can cause cataracts and glaucoma.
• Kidneys. Sarcoidosis can affect how your body handles calcium, which can lead to kidney failure.
• Heart. Granulomas in your heart can cause abnormal heart rhythms and other heart problems. In rare instances, this may lead to death.
• Nervous system. A small number of people with sarcoidosis develop problems related to the central nervous system when granulomas form in the brain and spinal cord. Inflammation in the facial nerves, for example, can cause facial paralysis.

“Sarcoidosis is a disease characterized by the growth of tiny collections of inflammatory cells (granulomas) in any part of your body — most commonly the lungs and lymph nodes. But it can also affect the eyes, skin, heart and other organs.

The cause of sarcoidosis is unknown, but experts think it results from the body’s immune system responding to an unknown substance. Some research suggests that infectious agents, chemicals, dust and a potential abnormal reaction to the body’s own proteins (self-proteins) could be responsible for the formation of granulomas in people who are genetically predisposed.”

MAYO CLINIC (https://www.mayoclinic.org/diseases-conditions/sarcoidosis/symptoms-causes/syc-20350358)

Sarcoidosis (pronounced SAR-COY-DOE-SIS) is an inflammatory disease characterized by the formation of granulomas, tiny clumps of inflammatory cells, in one or more organs of the body. When the immune system goes into overdrive and too many of these clumps form, they can interfere with an organ’s structure and function. When left unchecked, chronic inflammation can lead to fibrosis, which is permanent thickening or scarring of organ tissue.

This disorder can affect almost any organ in the body, including the heart, skin, liver, kidneys, brain, sinuses, eyes, muscles, bones, and other areas. Sarcoidosis most commonly targets the lungs and the lymph nodes, which are an important part of the immune system. When it affects the lungs, it is called pulmonary sarcoidosis. Ninety percent or more of people diagnosed with the disease have lung involvement.

Doctors believe sarcoidosis results from the body’s immune system responding to an unknown substance, most likely something inhaled from the air.

Symptoms in general to people affected by this disease sarcoidosis:

For many people, sarcoidosis begins with these symptoms in general:

NIH National Institute or Mental Health (https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd)

What disorders are related to ASD?

Certain known genetic disorders are associated with an increased risk for autism, including Fragile X syndrome (which causes intellectual disability) and tuberous sclerosis (which causes benign tumors to grow in the brain and other vital organs) — each of which results from a mutation in a single, but different, gene. Recently, researchers have discovered other genetic mutations in children diagnosed with autism, including some that have not yet been designated as named syndromes. While each of these disorders is rare, in aggregate, they may account for 20 percent or more of all autism cases.

People with ASD also have a higher than average risk of having epilepsy. Children whose language skills regress early in life — before age 3 — appear to have a risk of developing epilepsy or seizure-like brain activity. About 20 to 30 percent of children with ASD develop epilepsy by the time they reach adulthood. Additionally, people with both ASD and intellectual disability have the greatest risk of developing seizure disorder.

How is ASD diagnosed?

ASD symptoms can vary greatly from person to person depending on the severity of the disorder. Symptoms may even go unrecognized for young children who have mild ASD or less debilitating handicaps. Very early indicators that require evaluation by an expert include:

• no babbling or pointing by age 1
• no single words by age 16 months or two-word phrases by age 2.
• no response to name
• loss of language or social skills previously acquired
• poor eye contact
• excessive lining up of toys or objects
• no smiling or social responsiveness

Later indicators include:

• impaired ability to make friends with peers
• impaired ability to initiate or sustain a conversation with others
• absence or impairment of imaginative and social play
• repetitive or unusual use of language
• abnormally intense or focused interest
• preoccupation with certain objects or subjects
• inflexible adherence to specific routines or rituals

Health care providers will often use a questionnaire or other screening instrument to gather information about a child’s development and behavior. Some screening instruments rely solely on parent observations, while others rely on a combination of parent and doctor observations. If screening instruments indicate the possibility of ASD, a more comprehensive evaluation is usually indicated.

A comprehensive evaluation requires a multidisciplinary team, including a psychologist, neurologist, psychiatrist, speech therapist, and other professionals who diagnose and treat children with ASD. The team members will conduct a thorough neurological assessment and in-depth cognitive and language testing. Because hearing problems can cause behaviors that could be mistaken for ASD, children with delayed speech development should also have their hearing tested.

What causes ASD?

Scientists believe that both genetics and environment likely play a role in ASD. There is great concern that rates of autism have been increasing in recent decades without full explanation as to why. Researchers have identified a number of genes associated with the disorder. Imaging studies of people with ASD have found differences in the development of several regions of the brain. Studies suggest that ASD could be a result of disruptions in normal brain growth very early in development. These disruptions may be the result of defects in genes that control brain development and regulate how brain cells communicate with each other. Autism is more common in children born prematurely. Environmental factors may also play a role in gene function and development, but no specific environmental causes have yet been identified. The theory that parental practices are responsible for ASD has long been disproved. Multiple studies have shown that vaccination to prevent childhood infectious diseases does not increase the risk of autism in the population.

What role do genes play?

Twin and family studies strongly suggest that some people have a genetic predisposition to autism. Identical twin studies show that if one twin is affected, then the other will be affected between 36 to 95 percent of the time. There are a number of studies in progress to determine the specific genetic factors associated with the development of ASD. In families with one child with ASD, the risk of having a second child with the disorder also increases. Many of the genes found to be associated with autism are involved in the function of the chemical connections between brain neurons (synapses). Researchers are looking for clues about which genes contribute to increased susceptibility. In some cases, parents and other relatives of a child with ASD show mild impairments in social communication skills or engage in repetitive behaviors. Evidence also suggests that emotional disorders such as bipolar disorder and schizophrenia occur more frequently than average in the families of people with ASD.

In addition to genetic variations that are inherited and are present in nearly all of a person’s cells, recent research has also shown that de novo, or spontaneous, gene mutations can influence the risk of developing autism spectrum disorder.  De novo mutations are changes in sequences of deoxyribonucleic acid or DNA, the hereditary material in humans, which can occur spontaneously in a parent’s sperm or egg cell or during fertilization. The mutation then occurs in each cell as the fertilized egg divides. These mutations may affect single genes or they may be changes called copy number variations, in which stretches of DNA containing multiple genes are deleted or duplicated.  Recent studies have shown that people with ASD tend to have more copy number de novo gene mutations than those without the disorder, suggesting that for some the risk of developing ASD is not the result of mutations in individual genes but rather spontaneous coding mutations across many genes.  De novo mutations may explain genetic disorders in which an affected child has the mutation in each cell but the parents do not and there is no family pattern to the disorder. Autism risk also increases in children born to older parents. There is still much research to be done to determine the potential role of environmental factors on spontaneous mutations and how that influences ASD risk.

Do symptoms of autism change over time?

For many children, symptoms improve with age and behavioral treatment. During adolescence, some children with ASD may become depressed or experience behavioral problems, and their treatment may need some modification as they transition to adulthood. People with ASD usually continue to need services and supports as they get older, but depending on severity of the disorder, people with ASD may be able to work successfully and live independently or within a supportive environment.

How is autism treated?

There is no cure for ASD. Therapies and behavioral interventions are designed to remedy specific symptoms and can substantially improve those symptoms. The ideal treatment plan coordinates therapies and interventions that meet the specific needs of the individual. Most health care professionals agree that the earlier the intervention, the better.

Educational/behavioral interventions: Early behavioral/educational interventions have been very successful in many children with ASD. In these interventions therapists use highly structured and intensive skill-oriented training sessions to help children develop social and language skills, such as applied behavioral analysis, which encourages positive behaviors and discourages negative ones. In addition, family counseling for the parents and siblings of children with ASD often helps families cope with the particular challenges of living with a child with ASD.

Medications: While medication can’t cure ASD or even treat its main symptoms, there are some that can help with related symptoms such as anxiety, depression, and obsessive-compulsive disorder. Antipsychotic medications are used to treat severe behavioral problems. Seizures can be treated with one or more anticonvulsant drugs. Medication used to treat people with attention deficit disorder can be used effectively to help decrease impulsivity and hyperactivity in people with ASD. Parents, caregivers, and people with autism should use caution before adopting any unproven treatments