“Infertility is a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse.  Infertility affects millions of people – and has an impact on their families and communities. Estimates suggest that approximately one in every six people of reproductive age worldwide experience infertility in their lifetime.  In the male reproductive system, infertility is most commonly caused by problems in the ejection of semen (1), absence or low levels of sperm, or abnormal shape (morphology) and movement (motility) of the sperm.  In the female reproductive system, infertility may be caused by a range of abnormalities of the ovaries, uterus, fallopian tubes, and the endocrine system, among others.”

WHO World Health Organization (https://www.who.int/news-room/fact-sheets/detail/infertility)

“MERS-CoV infection refers to a viral respiratory illness called Middle East respiratory syndrome (MERS) that’s caused by a coronavirus (CoV).

Coronaviruses cause some cases of the common cold. But viruses in this group — such as MERS–CoV, SARS-CoV and SARS-CoV-2, which is the virus that causes COVID-19 — also cause serious illness.

MERS–CoV was first reported in Saudi Arabia. Since then, it’s been reported in other countries in the Middle East and in Africa, Europe, Asia and the United States. Most infections outside of the Middle East have been reported by people who recently traveled there.

MERS–CoV infection ranges from mild to severe.”.

MAYO CLINIC (https://www.mayoclinic.org/diseases-conditions/sars/expert-answers/what-is-mers-cov/faq-20094747)

“Currently, there is no cure for Creutzfeldt-Jakob disease (CJD). Researchers have tested many drugs, including acyclovir, amantidine, antibiotics, antiviral agents, interferon and steroids. None has shown consistent benefit.

“The best way to treat hemophilia is to replace the missing blood clotting factor so that the blood can clot properly. This is typically done by injecting treatment products, called clotting factor concentrates, into a person’s vein. Clinicians typically prescribe treatment products for episodic care or prophylactic care. Episodic care is used to stop a patient’s bleeding episodes; prophylactic care is used to prevent bleeding episodes from occurring. Today, it’s possible for people with hemophilia, and their families, to learn how to give their own clotting factor treatment products at home. Giving factor treatment products at home means that bleeds can be treated quicker, resulting in less serious bleeding and fewer side effects.”

Centers for Disease Control and Prevention – CDC (https://www.cdc.gov/ncbddd/hemophilia/treatment.html)

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.

Read MASAC’s recommendation on emicizumab.

• 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.

“One hundred years ago, at the time when Haematologica was first published, there was practically no treatment for the hemophilias or for the other inherited coagulation disorders. Whole blood was the only treatment approach available and this was of poor clinical efficacy, such that the life expectancy of hemophiliacs was 10-15 years, even in the most favorable circumstances.The success story of hemophilia care first began in the 1970s, when the availability of plasma-derived concentrates of coagulation factor VIII (FVIII) and factor IX (FIX) provided efficacious treatment of bleeding in patients with hemophilia A and B. This positive scenario was consolidated in terms of greater safety and availability in the 1990s, when the first recombinant coagulation factors were produced. This meant that, instead of only treating episodic bleeding events, prophylaxis regimens could be implemented as a preventive measure.  So, even until the 1960s, the life expectancy of patients with hemophilia was no more than 20-30 years.  Today success is way ahead.”

NIH – National Library of Medicine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049365/)

Treatment Breakthroughs

In the early 1900s, there was no way to store blood. People with hemophilia who needed a transfusion typically received fresh whole blood from a family member. Life expectancy was 13 years old.

In 1901, the US Surgeon General’s Catalogue listed lime, inhaled oxygen and the use of thyroid gland or bone marrow, or hydrogen peroxide or gelatin, as treatments for hemophilia. By the 1930s, it was discovered that diluting certain snake venoms caused blood to clot. These treatment  were used in patients with hemophilia.

By 1926, the US Surgeon General’s Catalogue contained an entire section on the use of blood transfusions to replace missing clotting factors. Physicians discovered that patients responded readily to infusions of plasma when given promptly after they sustained spontaneous joint and muscle bleeding.

In 1937 Harvard physicians Arthur Patek and FHL Taylor published a paper describing anti-hemophilia globulin found in plasma. It could decrease clotting time in patients with hemophilia.

By the late 1950s and early 1960s fresh frozen plasma was transfused in patients in the hospital. However, each bag of the plasma contained so little of the necessary clotting factor that huge volumes of it had to be administered. Many children experienced severe joint bleeds that were crippling. Intracranial hemorrhage could be fatal. By 1960, the life expectancy for a person with severe hemophilia was less than 20 years old.

A paper written by Robert Macfarlane, a British hematologist, in the journal Nature in 1964 described the clotting process in detail. The interaction of the different factors in blood clotting was termed the “coagulation cascade,” now called the clotting cascade.

In 1965, Dr. Judith Graham Pool, a researcher at Stanford University, published a paper on cryoprecipitate. In a major breakthrough, she discovered that the precipitate left from thawing plasma was rich in factor VIII. Because cryoprecipitate contained a substantial amount of factor in a smaller volume, it could be infused to control serious bleeding. Blood banks could produce and store the component, making emergency surgery and elective procedures for patients with hemophilia patients much more manageable.

By the 1970s, freeze-dried powdered concentrates containing factor VIII and IX became available. Factor concentrates revolutionized hemophilia care because they could be stored at home, allowing patients to “self-infuse” factor products, alleviating trips to the hospital for treatment.

By the mid-1980s, it was confirmed that HIV/AIDS could be transmitted through the use of blood and blood products, such as those used to treat hemophilia. Approximately half of the people with hemophilia in the US eventually became infected with HIV through contaminated blood products; thousands died. The overwhelming impact of HIV on the bleeding disorders community was felt into the next few decades.

The hepatitis C virus (HCV) infection was also transmitted through contaminated factor products, pooled from the blood of hundreds of thousands of donors. Before testing for HCV began in 1992, an estimated 44% of all people with hemophilia had contracted it. With the advent of more sophisticated screening methods and purification techniques, the risk of contracting HCV through factor products is virtually nil.

Treatment for hemophilia and other bleeding disorders advanced in the 1990s. Factor products became safer as tighter screening methods were implemented and advanced methods of viral inactivation were used. In addition, synthetic (not derived from plasma) factor products were manufactured using recombinant technologies. In 1992, the first recombinant factor VIII product was approved by the Food and Drug Administration (FDA). In 1997, the first recombinant factor IX product was granted FDA approval. Additional synthetic drugs, such as desmopressin acetate (DDAVP), were also introduced to treat mild-to-moderate hemophilia A and von Willebrand disease.

By 1995, prophylaxis, a preventive treatment regimen performed 2-3 times weekly in children with hemophilia, became more common. Since the advent of prophylaxis, most children in the developed world live with  less pain, without the orthopedic damage associated with chronic bleeding. As a result, most children born with hemophilia in the US today can look forward to long, healthy and active lives.

However, some children develop inhibitors, or antibodies, to infused factor product. The development of a bypassing agent in 1997 offered these patients an alternative product to help stop bleeds and joint damage.

The early years of the 21^st century have brought new recombinant products made without human or animal plasma derivatives, lowering the possibility risk for  allergic reactions to the products or inhibitors? New longer-lasting products promise to decrease regular  infusion rates from 2-3 times per week to once-weekly or even less.

In 2013, three separate gene therapy trials were begun at institutions across the country. They are testing the use of viruses as vector, or vehicles, to deliver factor IX genes into patients’ livers, correcting their hemophilia. Because the factor VIII gene is larger and more complicated to use, gene therapy clinical trials have not yet begun for patients with hemophilia A.

TIMELINE

1828 – Term “haemorrhaphilia” first used. Later shortened to “haemophilia.”

1926 – Erik von Willebrand identifies a bleeding disorder, later called von Willebrand disease (VWD)

1940s – whole blood transfusions given at hospital

1948 – National Hemophilia Foundation (NHF) opens as The Hemophilia Foundation, Inc.

1952 – Researchers describe what is now called factor IX clotting protein

1954 – NHF establishes a Medical Advisory Council, later called Medical and Scientific Advisory Council (MASAC)

1955 – First infusions of factor VIII in plasma form

1957 – Researchers in Sweden identify von Willebrand factor as the cause of VWD

1958 – First use of prophylaxis for hemophilia A

1964 – Dr. Judith Graham Pool discovers cryoprecipitate

1968 – First FVIII concentrate available

1970s – Primary prophylaxis therapy experiments begin

1970s – Freeze-dried plasma-derived factor concentrates available

1977 – Desmopressin identified to treat mild hemophilia and von Willebrand disease

1980s – Factor VIII, FIX and von Willebrand factor genes cloned

1982 – CDC reports first AIDS cases among people with hemophilia

1985 – First inactivated factor concentrates available

1992 – FDA approves first recombinant FVIII products

1995 – Prophylaxis becomes standard of treatment in US

1997 – FDA approves first recombinant FIX products

1998 – First human gene therapy trials begin

2000s – FDA approves first recombinant factor products made without human or animal plasma derivatives

2009 – FDA approves RiaSTAP to treat factor I deficiency

2011 – FDA approves Corifact to treat factor XIII deficiency

2013 – Gene therapy trials underway at three sites in the US

Check out a decade later 2023 treatments, tomorrow!

“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. Blood contains many proteins called clotting factors that can help to stop bleeding. People with hemophilia have low levels of either factor VIII (8) or factor IX (9). The severity of hemophilia that a person has is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur which can lead to serious health problems.”

Centers for Disease Control and Prevention (https://www.cdc.gov/ncbddd/hemophilia/facts.html)

“April is National Donate Life Month, a time when organizations raise awareness about organ and tissue donation programs.

Nationally, more than 100,000 people are currently awaiting an organ transplant, including about 5,000 people in the Greater Philadelphia region, according to Rick Hasz, CEO of Gift of Life, a local organ donation program.

Hasz said most waitlisted patients in the area are waiting on a new kidney, and that some people wait for more than five years.

“With kidney disease, you have dialysis that can kind of get you through until that transplant, but the mortality rate on dialysis is very high. And so some people never get that second chance,” Hasz said.”

WHYY PBS (https://whyy.org/articles/april-national-donate-life-month-organ-transplants-philadelphia/)

More than 400,000 Americans in every corner of our country are alive today thanks to the tremendous generosity and courage of organ donors. During National Donate Life Month, striveforgoodhealth.com honors donors and their families who have turned pain into purpose by sharing the gift of life with loved ones in need or countless others whom they have never met.  Those who came to the most challenge in their life and lives who thought of others to save them with their organs THANK YOU A MILLION TIMES!!  It is encouraged to everyone to follow their lead and register as an organ, eye, tissue, or bone marrow donor, bringing hope and healing to so many others.

The White House Blog (https://www.whitehouse.gov) states, ” Last year, American doctors completed our Nation’s one-millionth organ transplant, a tremendous milestone in the history of a procedure pioneered and honed in America. We are now performing transplants at a record pace, with higher success rates and increased lifespans for recipients. Still, every 10 minutes, someone new joins the waiting list — fighting organ failure or blood cancer, their futures hanging in the balance. More than 100,000 people, including 1,900 children, are currently on the waiting list. A majority of them are people of color, for whom it can sometimes be more difficult to find a good donor match. Seventeen Americans die every day while waiting for a transplant.”

Remember you have the power to change that. Just one person can save up to 8 lives through organ donation after they die and improve another 75 lives through eye and tissue donation. Registering as a donor does not change the quality of care that you receive in your lifetime. It allows you to give countless others a second chance at life and your family to find peace amid grief while leaving an extraordinary legacy of compassion and dignity.

Each year, thousands of Americans choose to donate an organ while still living, a profoundly courageous act of connection and healing.  Can you be an organ donor at the end of your life whenever that may come about in your lifetime to a save another one’s life rather than your good organs just disintegrate by nature after death?

Bless all donor organs and again thank you for thinking of others!