Treatment Options for Bleeding Disorders

There are many different types of therapies for bleeding disorders, and new ones are in development. Each person may respond to a treatment in their own way, so it is important to work closely with your hematologist to find a treatment that works for you.

Factor replacement therapies: Often referred to as “factor,” these products use a molecule that is either similar to natural factor found in humans (recombinant) or use an actual human molecule (plasma derived.) These treatments increase the amount of factor in the body to levels that lead to better clotting, and therefore less bleeding. The therapy is taken intravenously via an injection into a vein. This process is also called “infusion.” There are two types of factor replacement therapies: standard half-life (SHL) and extended half-life (EHL)

• Standard half-life therapies: Standard half-life therapies are used to treat hemophilia A and B, some types of von Willebrand disease, and some rare factor disorders. Dosing can be anywhere from three times a week to every day, depending on the person.
• Extended half-life (EHL) therapies: EHL contains a molecule that has been modified in some way to delay the breaking down of factor in the body. This results in higher levels of factor in the body lasting for longer, resulting in less frequent infusions. How long the factor is effective in the body depends on the person. Extended half-life therapies are mostly used to treat hemophilia A and B.
• Bypassing agents are used to treat bleeds in people with hemophilia with inhibitors. These treatments contain other factors that can stimulate the formation of a clot and stop bleeding.

Non-factor replacement therapies: These products help prevent bleeding or assist in better clotting using other methods in the body besides factor replacement therapy. Non-factor replacement therapies include:

• Emicizumab (Hemlibra) is a therapy used to treat hemophilia A, to prevent bleeding episodes in people both with and without inhibitors. It is known as a factor VIII(8) mimetic because it mimics, or imitates, the way factor VIII(8) works. It brings together factor IX(9) and factor X (10), which allows the blood to clot. Unlike factor replacement therapy, in which the missing factor is injected directly into a person’s vein (called an infusion), emicizumab is given by an injection under the skin, called a subcutaneous injection. Emicizumab was approved by the FDA to treat people with hemophilia A with inhibitors in 2017 and for people with hemophilia A without inhibitors in 2018.

• Desmopressin (DDAVP) is the synthetic version of vasopressin, a natural antidiuretic hormone that helps stop bleeding. In patients with mild hemophilia, it can be used for joint and muscle bleeds, for nose and mouth bleeds, and before and after surgery. It comes in an injectable form and a nasal spray. The manufacturer of DDAVP nasal spray issued a recall of all US products and does not expect to begin resupplying until 2022. DDAVP is used to treat von Willebrand disease and mild hemophilia A.
• Aminocaproic acid (Amicar) prevents the breakdown of blood clots. It is often recommended before dental procedures, and to treat nose and mouth bleeds. It is taken orally, as a tablet or liquid. MASAC recommends that a dose of clotting factor be taken first to form a clot, then aminocaproic acid, to preserve the clot and keep it from being broken down prematurely. This can be used to manage bleeding in people with hemophilia A, B and VWD.

Gene therapy is a way of treating a genetic disease or disorder by providing people with working copies of the gene to correct the disease or disorder. There are different approaches to gene therapy, including gene transfer and gene editing.

Currently, gene therapies for Hemophilia A and Hemophilia B work differently in the body and have different results. It is important that you work with your Hemophilia Treatment Center to learn more about gene therapy, to determine if you are eligible, to make certain you understand the risks and benefits, and to ensure you have the information you need to make the best decision for you.

2023 – HEMGENIX is administered as a one-time-only intravenous infusion— delivered in 1-2 hours in an outpatient setting.

• Each dosing kit is personalized to your patient’s weight

• HEMGENIX is delivered as a single dose of 2 mL/kg body weight*

• HEMGENIX does not contain preservatives. Use aseptic technique and proper engineering controls (eg, a biological safety cabinet or isolator) according to institutional policies during the preparation and administration of HEMGENIX.

Hemophilia B gene therapy has been approved by the FDA for the treatment of adults with hemophilia B who currently use factor IX (FIX) prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.

“The central nervous system is made up of the brain and spinal cord. The spinal cord comprises a bundle of nervous tissue and support cells that send messages from the brain to the rest of your body. But did you know that, on average, the spinal cord ceases growing at four years of age?

And while the brain may be done growing by your teenage years, it is not considered fully developed until your mid-to-late 20s. That’s because the prefrontal cortex, responsible for planning, prioritizing, and impulse control, is one of the final regions of the organ to mature. This helps explain why teens are more likely to make poor decisions and engage in potentially harmful behaviors without considering the short or long-term risks involved.

Additionally, once your brain is fully developed, it may become more difficult to accept new ideas and change behavior. Although the reasoning isn’t completely understood, research has shown that while adolescents see increases in social vitality and openness measures, these decrease with age.

It’s a myth that you only use 10% of your brain. Rather, neuroscience confirms that the brain is always active and firing even when you’re sleeping. Another common fallacy is that brain size determines how smart you are. Intelligence is determined by the number of synapses (or connections) between brain cells, not by brain girth.

Have you heard the myth is that the brain breaks down with age?  Well, know that some cognitive functions, such as memory, may decline as you get older, other mental skills, such as comprehension, vocabulary, conflict resolution, and emotional regulation, can improve. And research has shown that when the elderly keep their minds active by exercising their brains with crossword puzzles or games like Sudoku and bingo, their intelligence may also increase.”

Penn LPS (https://lpsonline.sas.upenn.edu/features/7-fascinating-facts-about-neuroscience-and-brain-how-well-do-you-know-your-brain)

“The American Cancer Society’s estimates for soft tissue sarcomas in the United States for 2024 are:

• About 13,590 new soft tissue sarcomas will be diagnosed (7,700 in males and 5,890 in females).
• About 5,200 people (2,760 males and 2,440 females) are expected to die of soft tissue sarcomas.

These statistics include both adults and children.

The most common types of sarcoma in adults are:

• Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma)
• Liposarcoma
• Leiomyosarcoma”

American Cancer Society (https://www.cancer.org/cancer/types/soft-tissue-sarcoma/about/key-statistics.html)

Soft tissue sarcoma symptoms:

Like many forms of cancer, soft tissue sarcoma symptoms may appear at a more advanced stage of the disease, or you might not notice any symptoms at all. Symptoms, if they are present, will also vary depending on the type of sarcoma and its location.

Signs of soft tissue sarcoma include:

A lump or mass is the most common soft tissue sarcoma sign. The lump will form in the area in which the tumor is growing, and it may be accompanied by some pain if it is pressing on a nerve or muscle. Even if the lump isn’t painful, if it continues to grow, or if it is located deep within an extremity or body cavity, consult your doctor.

Uncomfortable swelling is another sign of soft tissue sarcoma, especially when it is located in the arms and legs.

Limited mobility may be a symptom of soft tissue sarcoma. Some tumors can restrict motion, such as those found in the hip, knee, shoulder or hands.

Skin lesions can occur when a sarcoma tumor breaks through the skin.

Other symptoms may be signs of soft tissue sarcoma, because a sarcoma tumor can form almost anywhere in the body and can therefore affect a variety of organs. For example, sarcomas in the abdomen may cause abdominal pain, vomiting or constipation, while sarcomas in the uterus may cause vaginal bleeding and/or abdominal pain. With gastrointestinal stromal tumors (GISTs), you may feel full after eating only very small meals, or you may vomit blood or have dark bowel movements.

Diagnosing Sarcoma:

If your doctor thinks you may have a sarcoma, you’ll probably need a full exam and tests, including: A sample of cells from the tumor, called a biopsy. A plain x-ray to imaging tests, such as a CT scan, an ultrasound, an MRI, a PET (Positron Emission Tomography) to help see inside your body. A bone scan, if you might have osteosarcoma.  Also a biopsy-several types of biopsies are used to diagnose sarcomas..

Treatment of Soft Tissue Sarcoma:

Surgery is typically the primary treatment for soft-tissue sarcoma, used to remove tumors. Chemotherapy, radiation therapy and/or targeted therapy may also be recommended, either alone or in combination with surgery, depending on the stage and extent of the disease, along with other factors.

Surgery

The goal of surgery is to locate and completely remove the soft tissue sarcoma tumor. Our pathologists then examine the tumor to determine whether or not additional treatment is necessary, and to reduce the risk of recurrence.

Chemotherapy

Chemotherapy may be used in combination with surgery and radiation therapy to treat advanced-stage soft tissue sarcoma. Chemotherapy drugs work to either destroy cancer cells or impede their ability to grow and reproduce.

At our hospitals, we are developing innovative therapies personalized to the care of each soft tissue sarcoma patient. Our medical oncologists work closely with soft tissue sarcoma patients to determine if chemotherapy is an appropriate treatment option. Throughout your soft tissue sarcoma treatment, your care team continually monitors the effect of chemotherapy on the disease, with physical exams, blood tests, CT scans, MRI scans and chest X-rays and imaging.

Radiation therapy

Depending on the type of soft tissue sarcoma you have and the extent of the disease, your soft tissue sarcoma treatment plan may include radiation therapy. Though surgery is usually the main treatment approach for soft tissue sarcoma, radiation treatments may also be used before (neoadjuvant therapy) or following surgery (adjuvant therapy).

Targeted therapy

Unlike standard chemotherapy drugs, which may affect all cells in the body, targeted therapy drugs are designed to seek out and kill specific cancer cells while sparing surrounding healthy cells. Targeted cancer therapies may be used alone, in combination with other targeted therapy treatments or with other soft tissue sarcoma treatments, such as chemotherapy, radiation therapy and surgery. Among the drugs used in targeted therapy are so-called kinase inhibitors, which target specific protein receptors that help regulate cell growth.

“Sarcomas are rare cancers that develop in the bones and soft tissues, including fat, muscles, blood vessels, nerves, deep skin tissues and fibrous tissues. According to the National Cancer Institute, about 12,000 cases of soft tissue sarcomas and 3,000 cases of bone sarcomas are diagnosed in the U.S. each year. Bone sarcomas are more common among children while soft tissue sarcomas are more common in adults.”

John Hopkins Medicine (https://www.hopkinsmedicine.org/health/conditions-and-diseases/sarcoma#:~:text=Sarcomas%20are%20rare%20cancers%20that,in%20the%20U.S.%20each%20year.)

What is Sarcoma?

Sarcoma is a rare but deadly form of cancer affecting connective tissues such as fat, muscle, blood vessels, nerve, bone, deep skin and cartilage. There are roughly 15,000 new cases in the United States each year, with a very low median age of 36 (for bone sarcomas). Survival rates are low, even in comparison to other rare cancers. Rhabdomyosarcoma, a relatively common sarcoma, has a five-year survival rate of 65%, even if caught before metastasis. If caught after metastasis, the five-year survival rate lowers to approximately 30%. This is all to say that while sarcomas are rare, they are extremely devastating.

Sarcomas are a diverse and sporadic group of tumors that have minimal hereditary influence. They are generally classified into two major groups; the group of tumor-specific reoccurring genetic mutations via specific and aberrant chromosome translocation, and the group of non-reoccurring mutations which are based on severe genetic and chromosomal instability. Both groups have altered cell growth-factor signaling pathways. As a result, the introduction of drugs which can normalize growth-factor receptors and proteins are of great interest and the primary treatment given. With improvements in these drugs, it is believed that sarcoma can move from a deadly disease to a chronic but non-life-threatening disease.

Unfortunately, the specificity of the first group of sarcomas, where specific chromosomes are improperly translocated, can often permit the sarcoma to prevail after standard treatment. This is obviously problematic but, if overcome, could spark the development of a whole new field of cancer treatment. In other words, if scientists can discover how to isolate and guide specific chromosomal arrangement, they will able to address many of the hard to treat cancers of today.

With genetic engineering it is theoretically possible to prevent cancer before it begins. However, even without moving this far into the future, the improper chromosomal translocation can provide a sort of name-tagging of the cancer cell. With the cancer cells identified, it can guide modalities aimed at destroying diseased tissue while sparing healthy tissue.

Sarcoma is an under-researched cancer whose research can help to elevate cancer treatment, as a whole. Not only would breakthroughs save the lives of countless children, it could also advance medicine, as a whole. By bringing awareness to sarcoma and the potential development its research can spark, this potential can become a reality.

Soft tissue sarcomas may develop in any tissue that connects, supports or surrounds other structures and organs in the body. Some examples of where soft tissues sarcomas can develop are muscles, fascia (the tough membrane that surrounds muscles), tendons, fat, blood vessels, nerves and synovial tissues (connective tissue that makes up the membranes surrounding joints).

Soft tissue sarcomas are rare in adults, accounting for less than 1 percent of all new cases of cancer. The American Cancer Society reports that about 12,750 new cases of soft tissue sarcoma will be diagnosed in 2019 (7,240 cases in males and 5,510 cases in females). Sarcomas can be found almost anywhere in the body.

According to the National Cancer Institute, about 50 percent of soft tissue sarcoma cases occur in the extremities (arms and legs), 40 percent occur in the trunk (back and chest), and 10 percent occur in the head and neck.

Causes of Sarcoma:

“Cleft lip with or without cleft palate is among the most common of birth defects. The Centers for Disease Control and Prevention (CDC) estimates that in the United States:

• About 1 in every 1,600 babies is born with cleft lip with cleft palate.
• About 1 in every 2,800 babies is born with cleft lip without cleft palate.
• About 1 in every 1,700 babies is born with cleft palate.”

National Institute of Dental and Craniofacial Research (https://www.nidcr.nih.gov/health-info/cleft-lip-palate)

Health care providers are encouraged to provide women to plan for pregnancy; avoid harmful substances, like tobacco (2) and alcohol (3); and choose a healthy lifestyle, like eating a healthy diet (4), to increase their chances of a healthy pregnancy. Health care providers also discuss with women any medications they might be taking, both prescription and over-the-counter, to ensure they are taking only what is necessary. If yours is not maybe you need a new one. Prevention is the key to giving highier odds the baby will be healthier when born. Re-enforcement is a great tool and that’s where the medical profession comes into play with pregnant women who is their clientele.

Know that not all birth defects can be prevented. But, we also know that women can increase their chances of having a healthy baby by managing health conditions and adopting healthy behaviors before becoming pregnant. Make a commitment to yourself, to get healthy before and during pregnancy by actively trying to plan ahead, avoid harmful substances, choose a healthy lifestyle, and talk with your healthcare provider.   There are some that can be prevented.

1.Plan ahead.

Get 400 micrograms (mcg) of folic acid every day. Folic acid is a B vitamin. If a woman has enough folic acid in her body at least one month before and during pregnancy, it can help prevent major birth defects of the developing brain and spine defects like anencephaly or spina bifida. Anencephaly is a serious birth defect in which a baby is born without parts of the brain and skull. It is a type of neural tube defect (NTD). As the neural tube forms and closes, it helps form the baby’s brain and skull (upper part of the neural tube), spinal cord, and back bones (lower part of the neural tube). Spina bifida is a condition that affects the spine and is usually apparent at birth. It is a type of neural tube defect (NTD). Spina bifida can happen anywhere along the spine if the neural tube does not close all the way. The backbone that protects the spinal cord does not form and close as it should. This often results in damage to the spinal cord and nerves. Spina bifida might cause physical and intellectual disabilities that range from mild to severe. The severity depends on:

• The size and location of the opening in the spine.
• Whether part of the spinal cord and nerves are affected.
• There are 3 types and they are: 1-Myelomeningocele, 2-Meningocele, and 3-Spina Bifida Occulta.
• 1-Myelomeningocele is the most serious type of spina bifida. With this condition, a sac of fluid comes through an opening in the baby’s back. Part of the spinal cord and nerves are in this sac and are damaged. This type of spina bifida causes moderate to severe disabilities, such as problems affecting how the person goes to the bathroom, loss of feeling in the person’s legs or feet, and not being able to move the legs.
• 2-Meninocele is a sac of fluid comes through an opening in the baby’s back. But, the spinal cord is not in this sac. There is usually little or no nerve damage. This type of spina bifida can cause minor disabilities.
• 3-Spina bifida occulta is the mildest type of spina bifida. It is sometimes called “hidden” spina bifida. With it, there is a small gap in the spine, but no opening or sac on the back. The spinal cord and the nerves usually are normal. Many times, spina bifida occulta is not discovered until late childhood or adulthood. This type of spina bifida usually does not cause any disabilities.

1. • Women can get folic acid from fortified foods or supplements, or a combination of the two, in addition to a varied diet rich in folate.
   • See a healthcare professional regularly. A woman should be sure to see her doctor when planning a pregnancy and start prenatal care as soon as she thinks that she is pregnant. It is important to see the doctor regularly throughout pregnancy, so a woman should keep all her prenatal care appointments. If you are trying to have a baby or are just thinking about it, it is not too early to start getting ready for pregnancy. Use these checklists to help you write down your goals and have them in a place that you reinforce yourself to maintain them as best as possible for your child’s sake and your own sake as well.

2.Avoid harmful substances.

1. • Avoid alcohol at any time during pregnancy.                                    
   • Alcohol in a woman’s bloodstream passes to the developing baby through the umbilical cord. There is no known safe amount of alcohol use during pregnancy or while trying to get pregnant. There is also no safe time during pregnancy to drink. All types of alcohol are equally harmful, including wine and beer. Drinking alcohol during pregnancy can cause miscarriage, stillbirth, and a range of lifelong physical, behavioral, and These disabilities in the child, which occur because the mother drank alcohol during the pregnancy, are known as fetal alcohol spectrum disorders (FASDs). The best advice for women is to stop drinking alcohol when trying to get pregnant.
   • Avoid smoking cigarettes.
   • The dangers of smoking during pregnancy include preterm birth, certain birth defects from cleft lip or cleft palate to even infant death and more diseases inherited by mom through smoking. Even being around tobacco smoke puts a woman and her pregnancy at risk for problems. Quitting smoking before getting pregnant is best. For a woman who is already pregnant, quitting as early as possible can still help protect against some health problems for the baby, such as low birth weight. It’s never too late to quit smoking.
   • Avoid marijuana and other “street drugs”.
   • A woman who uses marijuana or other “street” drugs during pregnancy can have a baby who is born preterm, of low birth weight, or has other health problems, such as birth defects. Marijuana is the illicit drug most commonly used during pregnancy. Since we know of no safe level of marijuana use during pregnancy, women who are pregnant, or considering becoming pregnant, should not use marijuana, even in states where marijuana is legal. Women using marijuana for medical reasons should speak with their doctor about an alternative therapy with pregnancy-specific safety data.
   • Prevent infections.
   • Some infections that a woman can get during pregnancy can be harmful to the developing baby and can even cause birth defects. Some easy steps to prevent infections include frequent hand-washing, cooking meat until its well done, and staying away from people who have an infection. 

3.Choose a healthy lifestyle.

1. • Keep diabetes under control.
   • Poor control of diabetes during pregnancy increases the chances for birth defects and other problems for the pregnancy. It can also cause serious complications for the woman. Proper healthcare before and during pregnancy can help prevent birth defects and other poor outcomes.
   • Strive to reach and maintain a healthy weight.
   • Do you know …Your body mass index (BMI)? Calculate it. Where? Just look it up on the internet anywhere for free.

A woman who is obese (a Body Mass Index of 30 or higher) before pregnancy is at a higher risk for complications during pregnancy. Obesity also increases a pregnant woman’s risk of several serious birth defects. Even if a woman is not actively planning a pregnancy, getting healthy can help boost her health and her mood. If a woman is overweight or obese, she should talk with her doctor about ways to reach a healthy weight before she gets pregnant.

4.Talk with your healthcare provider.

1. • Talk to a healthcare provider about taking any medications.
   • We know that certain medications can cause serious birth defects if they are taken during pregnancy. For many medications taken by pregnant women, the safety has been difficult to determine. Despite the limited safety data, some medications are needed to treat serious conditions. If a woman is pregnant or planning a pregnancy, she should not stop taking medications she needs or begin taking new medications without first talking with her healthcare provider. This includes prescription and over-the-counter medications and dietary or herbal products.
   • Talk to a healthcare provider about vaccinations (shots).                                                

Most vaccinations are safe during pregnancy and some vaccinations, such as the flu vaccine and the Tdap vaccine (adult tetanus, diphtheria and acellular pertussis vaccine), are specifically recommended during pregnancy. Some vaccines protect women against infections that can cause birth defects. Having the right vaccinations at the right time can help keep a woman and her baby healthy. She should talk to her doctor about which vaccines are recommended for her during pregnancy.

ACPC-American Cleft Palate – Craniofacial Association addresses July the month of awareness to this condition with stating:

“Here are five key facts about clefts and craniofacial conditions, their impact and treatments:

1. Clefts are usually repaired surgically in the first year of life, though many children require additional surgeries and treatments through adolescence to correct challenges to breathing, eating or speech development.
2. Individuals born with cleft lip or palate often need specialized dental or orthodontic care throughout their lives as well.
3. There is no single factor related to the cause of cleft. Sometimes clefts run in families and in some cases have been linked to environmental factors.
4. Despite unique health challenges, those born with cleft and craniofacial conditions lead fulfilling, successful and accomplished lives.
5. Coordinated care is the best approach for successful surgical repair. Multidisciplinary teams approved by the ACPA are located across the nation and are comprised of qualified professionals from medical, surgical, dental, speech and allied health disciplines.”

“The causes of orofacial clefts among most infants are unknown. Cleft lip and cleft palate are thought to be caused by a combination of genes and other factors.

CDC research has found some factors that increase the risk of having a baby with an orofacial cleft:

• Smoking during pregnancy
• Having diabetes before pregnancy (type 1 or 2)
• Use of certain epilepsy medications during pregnancy”

CDC Birth Defects (https://www.cdc.gov/birth-defects/about/cleft-lip-cleft-palate.html)